Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression

Infectious Agents and Cancer

Jinlong Yan¹  Shouhua Zhang¹  Nuoya Li¹  Xin Yu¹  Yipeng Yang²  Junquan Zeng³  Jianping Lian³  Wen Chen⁴  Yanling Sheng⁵  Qiangliang Ma⁶ 

[1] Department of General Surgery, Second Affiliated Hospital of Nanchang University;Department of General Surgery, Xinhua Hospital of Shanghai Jiao Tong University School of Medicine;Department of Oncology, The Affiliated Hospital of Jinggangshan University;Department of Surgery, Jiangxi Provincial Cancer Hospital;Department of Ultrasound, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine;Department of dermatology, Ili Kazakh Autonomous State Chinese Medicine Hospital;

关键词: Hepatitis B virus;    cIAP2;    Sorafenib resistance;    Liver cancer;    Lamivudine;   

DOI  :  10.1186/s13027-021-00359-2

来源: DOAJ

【 摘 要 】

Abstract Background HBV promotes cell survival by upregulating the expression of the cellular inhibitor of apoptosis protein 2 (cIAP2), however whether it is involved in HBV-induced sorafenib resistance in liver cancer remains unclear. Methods cIAP2 overexpression and knockdown was adopted to assess the involvement of cIAP2 in HBV-induced sorafenib resistance. Anti-HBV drug lamivudine and Akt inhibitor were used to investigate the impact of HBV replication on cIAP2 expression and sorafenib resistance. Xenotransplantation mouse model was used to confirm the data on cell lines in vitro. Results Liver cancer cell line HepG2.215 showed increased cIAP2 expression and enhanced resistance to sorafenib. Upon sorafenib treatment, overexpression of cIAP2 in HepG2 lead to decreased cleaved caspase 3 level and increased cell viability, while knockdown of cIAP2 in HepG2.215 resulted in increased level of cleaved caspase 3 and decreased cell viability, suggesting the involvement of cIAP2 in HBV-induced sorafenib resistance. Furthermore, anti-HBV treatment reduced cIAP2 expression and partially restored sorafenib sensitivity in HepG2.215 cells. Xenotransplantation mouse model further confirmed that co-treatment with lamivudine and sorafenib could reduce sorafenib-resistant HepG2.215 tumor cell growth. Conclusion cIAP2 is involved in HBV-induced sorafenib resistance in liver cancer and anti-HBV treatments reduce cIAP2 expression and partially restore sorafenib sensibility.

【 授权许可】

Unknown