Chemotherapy resistance is one of the major challenges for the treatment of hepatocellular carcinoma (HCC). In order to investigate the mechanisms involved in chemoresistance of HCC, we established cisplatin (CDDP) and doxorubicin (Dox) resistant HCC cells. The expression of transcriptional coactivator with PDZ-binding motif (TAZ), one of the major downstream effectors of Hippo pathway, was upregulated in chemoresistant HCC cells. Targeted inhibition of TAZ via its siRNAs can restore CDDP and Dox sensitivity of chemoresistant HCC cells. The upregulation of TAZ increased the expression of IL-8 in HCC/CDDP and HCC/Dox cells. Recombinant IL-8 (rIL-8) antagonized the increased chemosensitivity mediated by TAZ knockdown. Mechanistically, TAZ can directly bind with the promoter of IL-8 to activate its transcription in chemoresistant HCC cells. Collectively, our data showed that TAZ-regulated expression of IL-8 was involved in chemoresistance of HCC cells. It indicated that targeted inhibition of TAZ/IL-8 axis might be helpful to improve chemotherapy efficiency for HCC.

化疗耐药性是治疗肝细胞癌（HCC）的主要挑战之一。为了研究参与肝癌化学耐药性的机制，我们建立了顺铂（CDDP）和阿霉素（Dox）耐药性HCC细胞。带有PDZ结合基序（TAZ）的转录共激活因子的表达，在河马的化学抗性HCC细胞中被上调。通过其siRNA靶向抑制TAZ可以恢复化学耐药性HCC细胞的CDDP和Dox敏感性。TAZ的上调增加了HCC / CDDP和HCC / Dox细胞中IL-8的表达。重组IL-8（rIL-8）拮抗了TAZ抑制介导的化学敏感性增加。从机理上讲，TAZ可以直接与IL-8的启动子结合，以激活其在化学抗性HCC细胞中的转录。总体而言，我们的数据表明TAZ调节的IL-8表达与HCC细胞的化学耐药性有关。这表明靶向抑制TAZ / IL-8轴可能有助于提高肝癌的化疗效率。