Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression.
Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression.
复制标题
B型肝炎病毒通过上调cIAP 2表达诱导肝癌索拉非尼B耐药
DOI：
10.1186/s13027-021-00359-2
复制
发表时间：
2021-03-23
影响因子：
3.7
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Zhang S;Li N;Sheng Y;Chen W;Ma Q;Yu X;Lian J;Zeng J;Yang Y;Yan J
HBV通过上调细胞凋亡抑制蛋白2（cIAP 2）的表达来促进细胞存活，然而其是否参与HBV诱导的肝癌中索拉非尼耐药仍不清楚。采用cIAP2过表达和敲低的方法来评估cIAP2在HBV诱导的索拉非尼耐药中的作用。采用抗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表现出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的过表达导致切割的caspase 3水平降低和细胞活力增加，而HepG2.215中cIAP2的敲低导致切割的caspase 3水平升高和细胞活力降低，表明cIAP2参与HBV诱导的索拉非尼耐药。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。cIAP2参与了肝癌中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。
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.
登录
查看更多内容
影响因子：
16
作者：
Menolfi D;Delamarre A;Lengronne A;Pasero P;Branzei D
通讯作者：
Branzei D
影响因子：
--
作者：
Ghouri YA;Mian I;Rowe JH
通讯作者：
Rowe JH
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
50.3
作者：
Lau, Chi-Chiu;Sun, Tingting;Wong, Nathalie
通讯作者：
Wong, Nathalie
影响因子：
3.3
作者：
Petrick, Jessica L.;McGlynn, Katherine A.
通讯作者：
McGlynn, Katherine A.