Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression
| Autor: | Yanling Sheng, Shouhua Zhang, Nuoya Li, Yipeng Yang, Xin Yu, Jinlong Yan, Jianping Lian, Qiangliang Ma, Wen Chen, Junquan Zeng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Sorafenib
Cancer Research Hepatitis B virus Epidemiology Caspase 3 Inhibitor of apoptosis urologic and male genital diseases lcsh:RC254-282 lcsh:Infectious and parasitic diseases 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Sorafenib resistance medicine heterocyclic compounds lcsh:RC109-216 Viability assay neoplasms 030304 developmental biology 0303 health sciences Gene knockdown business.industry medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens female genital diseases and pregnancy complications digestive system diseases Infectious Diseases Oncology Cell culture Lamivudine 030220 oncology & carcinogenesis Cancer research cIAP2 Liver cancer business medicine.drug Research Article |
| Zdroj: | Infectious Agents and Cancer, Vol 16, Iss 1, Pp 1-11 (2021) Infectious Agents and Cancer |
| ISSN: | 1750-9378 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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