Glycochenodeoxycholic acid induces stemness and chemoresistance via the STAT3 signaling pathway in hepatocellular carcinoma cells
Glycochenodeoxycholic acid induces stemness and chemoresistance via the STAT3 signaling pathway in hepatocellular carcinoma cells
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DOI：
10.18632/aging.103751
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发表时间：
2020-08-15
期刊：
影响因子：
5.2
通讯作者：
Zhu, Guoqing
中科院分区：
文献类型：
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作者：
Shi, Changying;Yang, Jiamei;Zhu, Guoqing
肝细胞癌（HCC）的预后不良主要是由于其高复发频率和化疗耐药。上皮-间充质转化（EMT）和癌症干细胞（CSCs）的获得是HCC化疗耐药的基本驱动因素。糖鹅脱氧胆酸（GCDC）是胆汁酸（BA）的一种成分，据报道可诱导人原代肝细胞坏死。在本研究中，我们探讨了GCDC在HCC化疗耐药中的作用。我们发现GCDC分别通过下调和上调凋亡和抗凋亡基因的表达来促进HCC细胞的化疗耐药。此外，GCDC诱导HCC细胞的EMT表型和干性，并激活STAT3信号通路。这些发现表明，GCDC通过STAT3途径诱导干细胞形成，从而促进HCC的化疗耐药，可能是HCC化疗的潜在靶点。
The poor prognosis of hepatocellular carcinoma (HCC) is primarily attributed to its high frequency of recurrence and resistance to chemotherapy. Epithelial-to-mesenchymal transition (EMT) and the acquisition of cancer stem cells (CSCs) are the fundamental drivers of chemoresistance in HCC. Glycochenodeoxycholic acid (GCDC), a component of bile acid (BA), has been reported to induce necrosis in primary human hepatocytes. In the present work, we investigated the function of GCDC in HCC chemoresistance. We found that GCDC promoted chemoresistance in HCC cells by down-regulating and up-regulating the expression of apoptotic and antiapoptotic genes, respectively. Furthermore, GCDC induced the EMT phenotype and stemness in HCC cells and activated the STAT3 signaling pathway. These findings reveal that GCDC promotes chemoresistance in HCC by inducing stemness via the STAT3 pathway and could be a potential target in HCC chemotherapy.