Knockdown of REG Iα Enhances the Sensitivity to 5-Fluorouracil of Colorectal Cancer Cells via Cyclin D1/CDK4 Pathway and BAX/BCL-2 Pathways.

Abstract

Objective: The reverse of chemoresistance and the improvement of sensitivity to chemotherapeutic agents of colorectal cancer cells have great clinical significance and the mechanism underlying the drug resistance is still unclear. REG Iα was reported to be upregulated in colorectal cancer tissues, but the roles of chemoresistance are still unclear. Materials and Methods: The expression of REG Iα in colorectal cancer cell lines was assessed by quantitative real-time polymerase chain reaction (Q-PCR). The expression of REG Iα in HCT116 and LOVO cells was knockdown by siRNA. The cell viability and IC50 (half maximal inhibitory concentration) values were analyzed by the CCK8 assay. The proportion of apoptosis and cell cycles were analyzed by flow cytometry. The migration potency of HCT116 and LOVO cells was analyzed by cell migration assay. The protein level of Cyclin D1, CDK4 (cyclin-dependent kinase 4), Bax and Bcl-2 were analyzed by western blot. Results: Knockdown of REG Iα enhances the sensitivity to 5-Fu of colorectal cancer cells. REG Iα knockdown promoted the cell apoptosis of HCT116 and LOVO under the 5-Fu treatment. The cell migration and cycle of colorectal cancer cells was also inhibited by REG Iα knockdown. We also found that REG Iα knockdown induced cell cycle arrest and cell apoptosis by Cyclin D1/CDK4 pathway and BAX/BCL-2 pathways. Conclusions: Knockdown of REG Iα enhances the sensitivity to 5-Fu of colorectal cancer cells via cyclin D1/CDK4 pathway and BAX/BCL-2 pathways.