Research Paper Volume 12, Issue 15 pp 15546—15555
Glycochenodeoxycholic acid induces stemness and chemoresistance via the STAT3 signaling pathway in hepatocellular carcinoma cells
- 1 Department of Hepatology, Eastern Hepatobiliary Surgery Hospital, Affiliated to Second Military Medical University, Shanghai, China
- 2 National Center for Liver Cancer, Second Military Medical University, Shanghai, China
- 3 Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Affiliated to Second Military Medical University, Shanghai, China
- 4 Department of Interventional Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Received: December 20, 2019 Accepted: July 6, 2020 Published: August 3, 2020
https://doi.org/10.18632/aging.103751How to Cite
Copyright © 2020 Shi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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 anti-apoptotic 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.