Brassicasterol inhibits hepatitis B virus-associated hepatocellular carcinoma development via suppression of AKT signaling pathway

Infectious Agents and Cancer

卷:18

Research

Shouhua Zhang¹  Xin Yu²  Jinlong Yan²  Junquan Zeng³  Jianping Lian³  Jindi Zeng⁴  Shuijiao Pang⁴  Jiancheng Wu⁴  Feifei Wang⁴ 

[1] Department of General Surgery, Jiangxi Provincial Children’s Hospital, 330006, Nanchang, Jiangxi Province, China;

[2] Department of General Surgery, Second Affiliated Hospital of Nanchang University, No1 Minde Road, 330006, Nanchang, Jiangxi Province, China;

[3] Department of Oncology, The Affiliated Hospital of Jinggangshan University, 343000, Ji’an, Jiangxi Province, China;

[4] Department of Pharmacy, The Affiliated Hospital of Jinggangshan University, 343000, Ji’an, Jiangxi Province, China;

关键词: Brassicasterol;    Hepatitis B virus;    Inhibition;    Hepatocellular carcinoma;   

DOI  :  10.1186/s13027-023-00502-1

 received in 2022-10-30, accepted in 2023-04-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHepatitis 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.MethodsThe 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.ResultsBrassicasterol 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 addition, brassicasterol showed similar levels of inhibition on HBV− and HBV + HCC cells.ConclusionBrassicasterol possesses anti-cancer activity against HCC through the downregulation of AKT pathway and such activity is independent of HBV infection.

【 授权许可】

CC BY   
© The Author(s) 2023

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