The Effects of siRNA-Mediated Gene Silencing of Alpha-7 Nicotinic Acetylcholine Receptors on Drug Resistance to Oxaliplatin in Colorectal Cancer Cells

The role of alpha-7 nicotinic acetylcholine receptor (α7nAchR) in colorectal cancer (CRC) chemoresistance, especially in Oxaliplatin (OXA)-resistant cells, has not yet been identified. Therefore, this study was performed to evaluate the impact of suppression of α7nAchR by specific siRNA on OXA-resistant cells. OXA-resistant SW-480 cells were established by raising the concentration of OXA and exposing cells repeatedly. Then, the electroporation method was used to transfer siRNA sequencing to cells to inhibit α7nAchR expression. IC50 values of OXA and the combination of specific siRNA for silencing of α7nAchR (α7-siRNA) and OXA were determined using the MTT assay. qRT-PCR was used to evaluate the expression of α7nAchR, MDR-1, Bcl-2, and Caspase-3 genes. The results indicated that suppression of α7nAchR expression could cause sensitization in OXA-resistant cells. This study also showed significant induction in α7nAchR mRNA expression in OXA-resistant cells compared to naïve cells. α7-siRNA transfection significantly reduced the expression of α7nAchR simultaneously with IC50 values. Also, following transfection with α7-siRNA, decreased expression of MDR-1 and Bcl-2 genes were observed along with increased expression of the Caspase-3 gene. According to the findings of this study, α7nAchR has a pivotal role in OXA chemosensitivity. Thus, α7nAchR may be considered a clinical marker in CRC drug resistance, and its suppression may be a potential therapeutic approach for CRC therapy.