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. 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. 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. cIAP2 is involved in HBV-induced sorafenib resistance in liver cancer and anti-HBV treatments reduce cIAP2 expression and partially restore sorafenib sensibility.

中文翻译：

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乙型肝炎病毒通过上调 cIAP2 表达诱导肝癌索拉非尼耐药


HBV 通过上调细胞凋亡蛋白抑制剂 2 (cIAP2) 的表达来促进细胞存活，但其是否参与 HBV 诱导的肝癌索拉非尼耐药尚不清楚。采用 cIAP2 过表达和敲低来评估 cIAP2 在 HBV 诱导的索拉非尼耐药中的作用。使用抗HBV药物拉米夫定和Akt抑制剂研究HBV复制对cIAP2表达和索拉非尼耐药的影响。使用异种移植小鼠模型来确认体外细胞系的数据。肝癌细胞系 HepG2.215 显示 cIAP2 表达增加和对索拉非尼的耐药性增强。索拉非尼治疗后，HepG2中cIAP2的过度表达导致cleaved caspase 3水平降低和细胞活力增加，而HepG2.215中cIAP2的敲低导致cleaved caspase 3水平增加和细胞活力降低，这表明cIAP2参与了HBV-诱导索拉非尼耐药。此外，抗 HBV 治疗降低了 HepG2.215 细胞中 cIAP2 的表达并部分恢复了索拉非尼的敏感性。异种移植小鼠模型进一步证实拉米夫定和索拉非尼联合治疗可以减少索拉非尼耐药的HepG2.215肿瘤细胞的生长。 cIAP2 参与肝癌中 HBV 诱导的索拉非尼耐药，抗 HBV 治疗可降低 cIAP2 表达并部分恢复索拉非尼敏感性。