Alpha7 nicotinic acetylcholine receptor expression in Sorafenib-resistant Hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC), the most prevalent kind of liver cancer, remains one of the world's main causes of death. The alpha7 nicotinic acetylcholine receptor (alpha 7nAchR) has been recognized to be overexpressed in malignancies and chemoresistance. Since little is known about the role of alpha 7nAchR expression in drug-resistant cells, this study was designed to investigate the effect of alpha 7nAchR suppression in combination with Sorafenib (SOR) on SOR-resistant HCC cells. First, SOR-resistant HCC cells were generated. To suppress the expression of alpha 7nAchR, cells were treated with SOR following siRNA transfection. qRT-PCR was used to examine the expression of alpha 7nAchR and apoptotic genes by evaluating the IC50 of SOR and the combination of alpha 7nAchR siRNA and SOR on the survival of resistant cells. Moreover, apoptosis, autophagy, and cell cycle analysis for resistant HCC cells were performed using flow cytometry. Cell migration and colony formation assays were also used for further confirmation. Our results suggest that inhibiting alpha 7nAchR can lead resistant HCC cells to become sensitive. Furthermore, when siRNA and SOR were treated together, HCC-resistant cells showed a considerable reduction in alpha 7nAchR mRNA gene expression. In addition, when alpha 7nAchR was downregulated in combination with SOR, migration and colony formation were inhibited. Apoptosis was triggered by modulating the expression of apoptotic target genes, and cell cycle arrest was observed in the G2-M and subG1 phases. Overexpression of alpha 7nAchR in SOR-resistant HCC cells suggests that it might be a therapeutic target for HCC cell resistance therapy.