Published online Jul 28, 2021. doi: 10.3748/wjg.v27.i28.4667
Peer-review started: March 19, 2021
First decision: June 3, 2021
Revised: June 4, 2021
Accepted: June 22, 2021
Article in press: June 22, 2021
Published online: July 28, 2021
Y-box binding protein 1 (YB-1) promotes the proliferation of tumor cells, inhibits apoptosis, and activates the expression of multidrug resistance genes in breast cancer, kidney cancer and other cancers. It can also promote the resistance of gefitinib in lung adenocarcinoma cells. The specific molecular mechanism of YB-1 mediating drug resistance in hepatocellular carcinoma (HCC) is still unclear.
The study will provide a basis for the application of YB-1 in sorafenib resistance of HCC.
To detect the expression of YB-1 in HCC tissues and cells, and explore the role and the potential mechanism of YB-1 in sorafenib resistance of HCC.
In this study, the authors examined the expression levels of YB-1 in cancer and corresponding paracancerous tissues of HCC patients, and clarified whether YB-1 was involved in sorafenib resistance in HCC by overexpressing and knocking down YB-1 in two kinds of hepatoma cell lines. Furthermore, a nude mouse liver cancer xenograft tumor model was established to verify the role of YB-1 in mediating sorafenib resistance in HCC in vivo. The signaling pathways involved in YB-1-mediated drug resistance in hepatocarcinoma cells were also screened and validated by digital expression profiling (DGE) technology.
YB-1 expression levels were significantly upregulated in both cancer tissues of HCC patients and human hepatoma cell lines. YB-1 could resist the effects of sorafenib on proliferation and apoptosis in hepatocarcinoma cells, which in turn mediated the resistance of HCC cells to sorafenib. YB-1 mediates sorafenib resistance in hepatocarcinoma cells through activating the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.
Knockdown of YB-1 can effectively inhibit the occurrence of sorafenib resistance, and can also enhance the inactivation of sorafenib on the PI3K/Akt signaling pathway. Therefore, YB-1 is a sorafenib resistance related gene.
Downregulation of YB-1 may be a new potential method for the treatment of advanced HCC, and it is expected to improve the efficacy of sorafenib in the treatment of advanced HCC patients.