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- Springer Journals
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- Copyright © The Author(s) 2023
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- 10.1186/s13027-023-00502-1
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Abstract
Background Hepatitis B virus (HBV )-associated hepatocellular carcinoma (HCC) does not respond well to current treatment options like sorafenib, and there is an urgent need for developing therapeutical strategies for HBV + HCC. Brassicasterol has previously shown anti-cancer and anti-viral activities, however, its value against HBV + HCC remains to be explored. Methods The inhibitory effect of brassicasterol and sorafenib was evaluated on HBV + HCC cell lines and xenograft mouse model. The cytotoxicity of brassicasterol on normal liver cells were measured by LDH assay. AKT agonist was used to identify the targeted signaling pathway by brassicasterol. Results Brassicasterol induced HBV + HCC cell death in a both dose-dependent and time-dependent manner, and such inhibition was more potent than sorafenib. Brassicasterol did not show apparent cytotoxicity to normal liver cells. Xenograft mouse model further confirmed the inhibitory effect of brassicasterol on the growth of HBV + HCC. Furthermore, signaling pathway analysis showed that brassicasterol-treated HBV + HCC cells had decreased level of phosphor-AKT expression while the addition of AKT agonist could counteract the inhibitory effect of brassicasterol on HCC, indicating that brassicasterol suppressed AKT pathway to exhibit anti-cancer activity in HBV + HCC cells. In addi- tion, brassicasterol showed similar levels of inhibition on HBV− and HBV + HCC cells. Conclusion Brassicasterol possesses anti-cancer activity against HCC through the downregulation of AKT pathway and such activity is independent of HBV infection. Keywords Brassicasterol, Hepatitis B virus, Inhibition, Hepatocellular carcinoma *Correspondence: Jinlong Yan yjl19880608@126.com Jianping Lian 27047843@qq.com Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Zeng et al. Infectious Agents and Cancer (2023) 18:22 Page 2 of 9 Background Materials and methods As one of the most prevalent cancers worldwide, hepa- Cells and drugs tocellular carcinoma (HCC) is a leading cause of can- Cell lines HepG2.215, PLC5, HepG2, LO2, AML12, and cer-related death, accounting for more than 780,000 FL83B were all purchased from the Type Culture Col- deaths every year [1, 2]. Various risk factors are associ- lection of the Chinese Academy of Sciences (Shanghai). ated with HCC, but hepatitis B virus (HBV) infection HepG2.215 and PLC5 are both HBV-positive (termed as tops the ranking list and are estimated to contribute to HBV + hereafter) HCC cell lines. HepG2.215 is a stably more than 60% of all HCC cases worldwide [2, 3]. HBV transfected with HBV, while PLC5 only secretes HBsAg infection is prevalent around the globe. Although vac- but does not support HBV replication. HepG2 is an HBV- cination against HBV has greatly reduced the infec- negative (termed as HBV- hereafter) HCC cell line. LO2, tion rate, there are still 5–10% of the population that AML12, and FL83B are normal immortalized hepato- remains unprotected due to waned immunity over time cytes. LO2 is human origin while AML12 and FL83B are [4]. In addition, the limited vaccination coverage is mouse origin. accountable for a major portion of new HBV infections HepG2, HepG2.215, PLC5 and LO2 were cultured in [5]. Currently, approximately 257 million people are high glucose DMEM (Sangon) supplemented with 10% living with chronic HBV infection and 25 – 40% % of FBS (Hyclone) and penicillin (100 U/ml) and strepto- them have the lifetime risk of developing adverse out- mycin (100 µg/ml) (Sangon). AML12 cells were cultured comes HCC or cirrhosis [6, 7]. in DMEM/F12 medium (Sangon) supplemented with Currently, the common treatment options for early- 10% FBS, 10 µg/mL insulin (ThermoFisher Scientific), stage HCC are still surgical resection, liver transplan- 5.5 µg/mL transferrin (ThermoFisher Scientific), 5 ng/ tation and radiofrequency ablation [8, 9]. However, in mL sodium selenite (ThermoFisher Scientific), 40 ng/mL HBV + HCC patients, the recurrence rate is high after (100 nM) dexamethasone (ThermoFisher Scientific) and such treatments [1, 9]. The treatment options for late- antibiotics. FL83B cells were cultured in F-12K medium stage HCC are very limited, because conventional sys- (Procell) supplemented with 10% FBS and antibiot- temic chemotherapy offers unsatisfactory benefit [8]. The ics. Brassicasterol (cat no: B4936) was purchased from main options for late-stage HCC patients are multiki- Sigma-Aldrich, Merck and sorafenib (cat no: sc-220125) nase inhibitors like sorafenib, lenvatinib and regorafenib was purchased from Santa Cruz and AKT agonist IGF-1 etc. [8–10]. Sorafenib, a multikinase inhibitor, can sup- (cat no: ab9573) was purchased from Abcam. press cancer cell growth by promoting apoptosis and mitigating angiogenesis [11]. Although survival benefits Cell culture and drug treatment have been observed in HCC patients after treatment Cells were preseeded at 4 × 10 cells/well into 96 well with these drugs, the responses are not usually durable plates 16–18 h before drug treatment, and drugs were because of the rapid developed drug resistance [9, 12]. introduced by replacing old cell culture medium with Moreover, it has been revealed in several clinical trials fresh medium supplemented with drugs at desired con- that HBV + HCC patients do not respond well to multiki- centrations. For drug dose response tests, cells were nase inhibitors like sorafenib comparing to patients with- treated with sorafenib or brassicasterol at 0, 5, 10, 25 out HBV infection [13, 14]. Therefore, there is an urgent and 50 µM (HCC cells) or 0, 5, 10, 20, 40, 80, 160, 320, need for developing novel therapeutical strategies for 640 and 1280 µM (normal liver cells) for 48 h before cell HBV + HCC. viability or cytotoxicity was determined. For drug time Brassicasterol (24-methyl cholest-5,22-dien-3β-ol; course response tests, cells were treated with 10 µM C28H46O) is a type of phytosterol mainly produced by sorafenib or brassicasterol for up to 96 h, before cell via- unicellular algae and some terrestrial plants like rape [15]. bility or cytotoxicity was determined. For AKT agonist This natural product has been widely used as a food addi - treatment, AKT agonist IGF-1 was introduced into the tive and is known for its cardiological health benefits [16, cell culture 6 h before the treatment of brassicasterol and 17]. Recently, bassicasterol has been reported to show remained in the culture till the cell viability assay. anti-cancer and anti-viral activities [18–21]. However, its value in treatment for HCC, especially HBV + HCC, has Cell viability assay not yet been investigated. MTT assay was used to assess cell viability in this study In the current study, we investigated the therapeu- using a commercial MTT kit (Abcam), as previously tic value of brassicasterol against HBV + HCC both described with modifications [1]. In brief, cells in 96 well in vitro and on a xenograft mouse model. We also fur- plates were first treated as described above, and then cell ther explored the mechanism of action of brassicasterol culture medium was removed and 100 µl of MTT reagent against HBV + HCC. and serum-free medium at 1:1 ratio into each well. The Z eng et al. Infectious Agents and Cancer (2023) 18:22 Page 3 of 9 plates were then incubated at 37 °C for 3 h. After incuba- the gel separated proteins were then transferred onto a tion, 150 µl/well of MTT solvent was added and the plate PVDF membrane. The membrane was then sequentially was then shaken for 15 min on an orbital shaker at room blocked in 5% non-fat milk for 1 h at room temperature, temperature. Finally, plates were read at OD590 and cell and primary antibodies over night at 4 °C and HRP-con- viability was calculated with cells without drug treatment jugated secondary antibodies for 1 h at room tempera- considered 100% viable. ture, respectively. Following extensive washes with PBST, the membrane was incubated with ECL Plus Western Cytotoxicity assay Blotting Substrate (BosterBio) and immuno-bands were LDH assay was used to assess drug cytotoxicity in this imaged by a CCD camera. Semiquantification of the study with a commercial LDH assay kit (Abcam) fol- bands were achieved by Image J (Version 1.8.0; National lowing the manufacturer’s instructions. In brief, cells in Institute of Health, USA). The following primary anti - 96 well plates were first treated as described above, and bodies were used: Rabbit anti-cleaved Caspase 3 (ab2302; then plate gently shaken on an orbital shaker for 5 min Abcam), mouse anti-AKT antibody (60203-2-Ig; Protein- to ensure even distribution of LDH. After shaking, plates Tech), rabbit anti-p-AKT antibody (4060; Cell Signalling were centrifuged to pellet cells and 10 µl/well of the clear Technology), rabbit anti-ERK1/2 antibody (51068-1- medium were transferred to a new 96 plate, mixed with AP; ProteinTech), rabbit anti-p-ERK1/2 antibody (9101; 100 µl/well LDH reaction mix. The plates were then incu - Cell Signalling Technology) and mouse anti-GAPDH bated for 30 min at room temperature and then read antibody (60004-1-Ig; ProteinTech). The following sec - at OD450 (testing wavelength) and OD650 (reference ondary antibodies were used: HRP-conjugated goat wavelength). anti-rabbit IgG(H + L) (SA00001-2; ProteinTech) and HRP-conjugated goat anti-mouse IgG(H + L) (SA00001- Ethical statement 1; ProteinTech). All experimental protocols involving animals were reviewed and approved by the Ethical Review Commit- Statistical analysis tee of the Affiliated Hospital of Jinggangshan University All data were expressed as mean ± standard deviation (Approval Number: LUNLI-2022-002) and performed in (SD). Kruskal–Wallis test followed by Dunn’s multiple accordance with the local regulations. comparisons test were used to identify the statistical sig- nificance between groups and p value less than 0.05 was Tumor cell injection and drug treatment considered statistically significant. All statistical analyses The xenograft HCC mouse study was reviewed and were performed with GraphPad Prism (version 9.4.0). approved by the institutional ethical review committee and performed as previously described with modifica - Results tions [1]. In brief, HepG2.215 cells were first washed and The inhibitory effect of brassicasterol on HBV + HCC cells resuspended in PBS at 2 × 10 cells/ml, and then injected To test the anti-cancer effect of brassicasterol on 300 µl cell suspension under the skin at the left flank. HBV + HCC, 2 HBV-associated HCC cell lines, PLC5 When the tumor volume reached 100 mm , mice were and HepG2.215, were used in the current study. The 2 cell treated intraperitoneally with brassicasterol or sorafenib lines were first treated with increasing doses of brassicas - both at 100 mg/kg every day for 15 days. For mock treat- terol or the FDA-approved anti-HCC drug, sorafenib, ment, mice received equal volume of the same solvent as for 48 h, and then cell viability was assessed. As shown the drug treatment group. Tumor size and mouse weight in Fig. 1A–B and Figure S1A-B, both brassicasterol and were measured every 3 days. Tumor volume was calcu- sorafenib exhibited inhibitory effects on the viability 3 π lated using (meandiameter) × . Tumors were also of both HCC cell lines in a dose-dependent manner. Of weighed at the time of animal sacrifice. note, brassicasterol induced much more cell death than sorafenib at the same dose, indicating that brassicasterol Western blot has more potent anti-cancer effect than sorafenib against Western blot was performed as previously described HBV + HCC. with modifications [22]. In brief, cells were first mock In addition to the dose–response evaluation, a time- treated or treated with brassicasterol for 48 h, and then course response for brassicasterol against HBV + HCC cells were lysed with Pierce IP lysis buffer (Thermo Fisher cells were also conducted. PLC5 and HepG2.215 cells Scientific) supplemented with Protease phosphatase were treated with 10 µM brassicasterol or sorafenib inhibitors (Cell Signalling Technology). Centrifugation and cell viability was assessed at 0, 24, 48, 72 and 96 h. cleared cell lysates were then mixed with loading buffer Similar to the dose–response evaluation, both drugs and loaded onto an SDS-PAGE gel. After electrophoresis, reduced viability of both HCC cell lines in an incubation Zeng et al. Infectious Agents and Cancer (2023) 18:22 Page 4 of 9 Fig. 1 Brassicasterol promotes HBV + HCC cell cytotoxicity. A PLC5 and B HepG2.215 cells were incubated with increasing doses of brassicasterol or sorafenib for 48 h and cytotoxicity was assessed by LDH assay. C PLC5 and D HepG2.215 cells were incubated with 10 µM brassicasterol or sorafenib for up to 96 h and cytotoxicity was assessed by LDH assay. Data shown are mean ± SD of three independent experiments time-dependent manner, with brassicasterol showing Fig. 2B and S2B, all 3 normal liver cell lines did not show stronger impact on cell viability (Fig. 1C–D and Addi- apparent cell death induced by brassicasterol, while tional file 1: Fig. S1C–D). HBV + HCC cell line PLC5 showed almost 100% cell Taken together, our data here indicate that brassicast- death after 24 h of incubation with brassicasterol at this erol has anti-cancer activity against HBV + HCC and its concentration. These data indicate that brassicasterol is activity is stronger than FDA-approved drug sorafenib not toxic to healthy normal liver cells. in vitro. Brassicasterol suppresses the growth of HBV + HCC Cytotoxicity of brassicasterol on normal liver cells on the xenograft mouse model. In general, an ideal anti-cancer drug should specifically A study on a xenograft mouse model was also performed kill the cancer cells without causing damage on healthy to further explore the therapeutic value of brassicasterol cells. To test the cytotoxicity of brassicasterol to normal on HBV + HCC. Mice bearing xenografted HepG2.215 liver cells, normal non-tumor hepatocyte cell lines LO2, cell-derived tumor were either mock-treated, or treated AML2 and FL83B were used. Cells were first treated with with brassicasterol or sorafenib. As shown in Fig. 3A–B, increasing doses of brassicasterol for 48 h and then cyto- sorafenib treatment also showed marginal effect on the toxicity was assessed by LDH assay (Fig. 2) and MTT inhibition of tumor growth, while brassicasterol sig- assay (Additional file 1: Figure S2). Our data showed nificantly reduced the tumor volume. Similarly, tumor that a concentration up to 1280 µM of brassicasterol weight from mice treated with brassicasterol was signifi - did not show apparent cytotoxicity to normal liver cells cantly lower than that from mice received mock treat- after 48 h incubation while a dose-dependent cell death ment or sorafenib treatment (Fig. 3C). Mice weight did was detected in HBV + HCC cell line PLC5 (Fig. 2A and not show any apparent change from all groups (Fig. 3D). Additional file 1: Fig. S2A). To further explore the effect of long incubation time of brassicasterol on the health Brassicasterol inhibits HBV + HCC growth via AKT pathway of normal liver cells, these cell lines were incubated with AKT and ERK pathways are the common pathways 1000 µM brassicasterol for up to 96 h and cytotoxic- involving tumorigenesis and targeting these pathways ity was assessed at 0, 24, 48, 72 and 96 h. As shown in are proven to be effective against several cancers [23, Z eng et al. Infectious Agents and Cancer (2023) 18:22 Page 5 of 9 Fig. 2 Brassicasterol has minimal cytotoxicity to normal liver cells. A Normal liver cell lines LO2, AML2 and FL83B cells together with control HCC cell line PLC5 were first incubated with various doses of brassicasterol for 48 h and then cell cytotoxicity was assessed by LDH assay. B Cells were incubated with 1000 µM brassicasterol for up to 96 h and cell cytotoxicity was assessed by LDH assay. Data shown are mean ± SD of three independent experiments 24]. In addition, previous study has shown that bras- In addition, we also investigated whether the anti-HCC sicasterol inhibited prostate cancer growth by target- activity of brassicasterol was HBV infection dependent ing AKT pathway [19]. To investigate if brassicasterol or independent. HepG2 (HBV-) and HepG2.215 (HBV+) suppressed the growth of HBV + HCC through down- cells were first treated with increasing doses of brassi - regulation of one or both pathways, western blot was casterol or sorafenib, and the cell viability was assessed. performed. Our data showed that in HepG2.215 cells, In agreement with previous findings, sorafenib induced p-AKT and p-ERK1/2 were expressed in high lev- considerably more cell death in HBV- HepG2 cells than els, indicating the activated AKT and ERK pathways HBV + HepG2.215 cells (Fig. 5). However, such difference (Fig. 4A–B). Upon brassicasterol treatment, the level of was not observed in brassicasterol-treated cells, because p-AKT, but not p-ERK1/2, was considerably reduced, equivalent levels of cell death was detected in both together with increased expression of cleaved caspase HepG2 and HepG2.215 cells (Fig. 5). These data indi - 3, an indicator of cell apoptosis (Fig. 4A–B). cate that the anticancer activity of brassicaseterol against To further confirm that AKT pathway was targeted by HCC is HBV infection independent. brassicasterol in HCC inhibition, PLC5 and HepG2.215 cells were treated with brassicasterol in the presence or Discussion absence of AKT agonist. Our data showed that in the The development of curative treatment for HBV + HCC presence of AKT agonist, the anti-HCC effect was com - remains a challenge, due to several factors. First, promised in both cell lines (Fig. 4C–D). More impor- although treatment options for HBV infections are avail- tantly, the AKT agonist exhibited a dose-dependent able, there is still no cure [25]. Second, there is a high effect in rescuing cell viability of both HCC cell lines recurrence rate of neoplastic lesions for patients who (Fig. 4C–D). These data here indicate that brassicast - received resection surgery [26, 27]. Third, HBV + HCC erol inhibits HBV + HCC cell growth through suppres- responds less well to current treatment options, like sion of the AKT pathway. multikinase inhibitors [9, 12, 28]. Our previous studies Zeng et al. Infectious Agents and Cancer (2023) 18:22 Page 6 of 9 Fig. 3 Brassicasterol inhibits HBV + HCC xenografted tumor growth in mice. Nude BLAB/c mice bearing xenografted HepG2.215-derived tumors were either mock-treated or treated with sorafenib or brassicasterol for 15 days. A Tumor volumes were measured every 3 days for up to 15 days since the treatment. , p < 0.05. B Tumor sizes and C tumor weights on the day of animal sacrifice (day 16) were shown. ns, not statistically significant; * ** , p < 0.05; , p < 0.01. Scale bar: 1 cm. D Mice were weighed every 3 days for up to 15 days since the treatment have shown that HBV infection could promote HCC sorafenib, demonstrated comparable levels of inhibition survival and also induce resistance to multikinase inhibi- on both HepG2 and HepG2.215 cells, indicating that tor sorafenib via AKT signaling pathway [1, 29]. Poten- the anti-HCC activity of brassicasterol is independent tially, targeting the AKT signaling pathway could restrict of HBV infection (Fig. 5). Although further studies are HCC survival and reverse sorafenib resistance. In our required to characterize the activity of brassicasetrol on current study, brassicasterol inhibited HCC growth HBV + HCC, brassicasterol may serve as a novel treat- both in vitro on cell lines and also in xenograft mouse ment option for patients with developed resistance to model. And interestingly, the anti-HCC activity of bras- multikinase inhibitor drugs like sorafenib. sicasterol was via the suppression of the AKT signaling Brassicasterol has been long used as a food additive, pathway, indicating the importance of AKT pathway in however, its therapeutic values in various diseases have HBV + HCC. In addition, our data showed that brassicas- only been studied very recently. Brassicasterol has shown terol exhibited more potent activity against HBV + HCC anti-viral and anti-cancer activities, but the underlying than sorafenib. We also compared the anti-HCC activi- mechanisms are reported to be different to different dis - ties of brassicasterol and sorafenib on both HBV- and eases [18–21]. Its anti-HSV and anti-ADV activities are HBV + HCC cells, and in agreement with previous find - through inhibition of viral replication, its anti-bladder ings, sorafenib showed much stronger inhibitory effect cancer activity is through the inhibition of androgen on HBV- HCC cell line HepG2 than HBV + HCC cell line signaling pathway, while its anti-prostate cancer activ- HepG2.215 (Fig. 5). Interestingly, brassicasterol, unlike ity is through the inhibition of both androgen and AKT Z eng et al. Infectious Agents and Cancer (2023) 18:22 Page 7 of 9 Fig. 4 Brassicasterol inhibits HBV + HCC cell growth through AKT signaling pathway. A–B HepG2.215 cells were first either untreated, mock-treated or treated brassicasterol for 48 h and then the expression cleaved caspase 3, AKT, p-AKT, ERK1/2 and p-ERK1/2 was measured by western blot. A One representative data of three is shown. B Densitometry analysis of western blot data was performed with Image J. Data shown are mean ± SD of three independent experiments. C PLC5 and D HepG2.215 cells were either mock-treated or treated with brassicasterol in the presence or absence of AKT agonist for 48 h, and then cell viability was assessed by MTT assay. Data shown are mean ± SD of three independent experiments. , p < 0.05; ** *** , p < 0.01; , p < 0.001 signaling pathways [18–21]. In our study, we discovered AKT, a serine/threonine kinase, serves as a cen- that brassicasterol exhibited anti-HBV + HCC activity, tral node for many signaling pathways and plays an and such activity was AKT pathway dependent. Given important role in cell survival, proliferation, migra- the depth of research on brassicasterol until now, it is tion, metabolism and angiogenesis [30]. AKT pathway hard to interpret the mechanism of action for brassicast- is frequently dysregulated in many types of cancers[31]. erol’s broad anti-viral and anti-cancer activities. It is war- AKT itself is also considered an oncogene, and its over- ranted, however, for future studies to further investigate expression and over-activation are two of the major whether a single target by brassicasterol resulted in such events detected in various cancers [32, 33]. Therefore, anti-viral and anti-cancer activities effecting via various AKT has been investigated as a therapeutic target for downstream pathways. treatment of various cancers. AKT was targeted by Zeng et al. Infectious Agents and Cancer (2023) 18:22 Page 8 of 9 Fig. 5 The anti-HCC effect of brassicasterol and sorafenib on HBV + and HBV- HCC cells. HBV- HCC cell line HepG2 and HBV + HCC cell line HepG2.215 were incubated with increasing doses of A brassicasterol or B sorafenib for 48 h and cell viability was assessed by MTT assay. Data shown are mean ± SD of three independent experiments brassicasterol in HBV + HCC in our current study and Supplementary Information in prostate cancer in a previous study [19]. Although The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s13027- 023- 00502-1. it is beyond the scope of our current study, it worth to investigate if brassicasterol could inhibit the growth Additional file 1. Supplementary materials. of other types of cancers and whether targeting AKT pathway was the underlying mechanism. Acknowledgements In addition to in vitro testing on cell lines, we have Not applicable. also confirmed the anti-HCC activity of brassicasterol Author contributions on a xenograft mouse model, and consistent results JDZ, JY and JL designed the study. JZ, JW, SP, FW, XY, SZ, and JQZ performed were obtained from both in vitro and mouse study. and analysed the data. JDZ, JY and JL wrote the manuscript. All authors read Because this cell ectopic xenograft model is easy to and approved the final manuscript. establish at low cost and can also generate reliable Funding results rapidly, it is a compelling model for solid can- This work was supported by the National Natural Science Foundation of China cer research, especially for anticancer drug screening (No:81960443; 82260570), Jiangxi Provincial Education Department Scientific Research Foundation (GJJ211029), Jiangxi Provincial Health Technolgy [9, 29, 34]. Although being one of the widely used mod- Project (202210961) and Beijing KeChuang Medical Development Foundation els in HCC research, the xenograft mouse model has its (KC2021-JX-0186-125). limitations [34]. Because cancer cells are injected into Availability of data and materials nude mice subcutaneously, the xenograft model fails to The raw data supporting the conclusions of this manuscript will be made reflect the dynamic process of tumor-immune surveil - available by the authors, without undue reservation, to any qualified lance (34). Although beyond the scope of our current researcher. study, it would be warranted to confirm the anti-HCC activity on another animal model with intact animal or Declarations humanized immune system, before moving the study Ethics approval and consent to participate into clinical settings. All experimental protocols involving animals were reviewed and approved by the Ethical Review Committee of the Affiliated Hospital of Jinggangshan University (Approval Number: LUNLI-2022-002) and performed in accordance with the local regulations. Conclusion Our study has shown that brassicasterol has anti-can- Consent for publication Not applicable. cer activity against HBV + HCC and such activity is stronger than the FDA-approved drug sorafenib. Bras- Competing interests sicasterol inhibits the growth of HCC through the sup- The authors declare that they have no competing interests. pression of AKT signaling pathway and the inhibitory Author details effect on HCC is independent of HBV infection. Department of Pharmacy, The Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China. Department of General Surgery, Second Affiliated Hospital of Nanchang University, No1 Minde Road, Nan- Abbreviations chang 330006, Jiangxi Province, China. Department of General Surgery, HBV Hepatitis B virus Jiangxi Provincial Children’s Hospital, Nanchang 330006, Jiangxi Province, HCC Hepatocellular carcinoma Z eng et al. Infectious Agents and Cancer (2023) 18:22 Page 9 of 9 China. 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Journal
Infectious Agents and Cancer – Springer Journals
Published: Apr 20, 2023
Keywords: Brassicasterol; Hepatitis B virus; Inhibition; Hepatocellular carcinoma