The role of autophagy in the treatment of colon cancer by chlorin e6 photodynamic therapy combined with oxaliplatin

Abstract

BackgroundPhotodynamic therapy is a tumour treatment method. Its mechanism mainly induces apoptosis, autophagy, and other ways to cause cell death. Therefore, this study aims to evaluate the therapeutic effect of chlorine e6 photodynamic therapy (Ce6-PDT) combined with oxaliplatin (L-OHP) in colon cancer and to investigate the role of autophagy in L-OHP treatment and Ce6-PDT combined with L-OHP in colon cancer. MethodsCCK-8 assay, Scratch wound healing assay, and Western Blot (WB) were used to identify drug-resistant colon cancer cell line SW620/L-OHP. Annexin V/FITC assay, laser confocal double immunofluorescence staining method and WB were employed to investigate the apoptosis and autophagy changes in Ce6-PDT combined with L-OHP. ResultsDrug resistance cells SW620/L-OHP were developed under the continuous multi-generation of L-OHP treatment, and the expression of ATP-binding cassette subfamily B member 1 (ABCB1) and ATG5 proteins were increased. The results of immunofluorescence showed that LC3B accumulated in SW620 cells and SW620/L-OHP cells under the treatment of L-OHP. The WB results indicated that LC3B and ATG5 protein expression was increasing in SW620 cells and SW620/L-OHP cells. Inhibition of L-OHP-induced autophagy reduces SW620 cells and SW620/L-OHP cells’ viability while increasing apoptosis and the Pro Caspase-3 protein expression. The combination of Ce6-PDT and L-OHP decreased the cell viability, the cell migration ability, the Bcl-2 protein expression, and increased the apoptosis rate, Pro Caspase-3 protein expression in SW620 cells. ConclusionsL-OHP can cause SW620 cells drug resistance. Autophagy plays a protective role in the L-OHP treatment of SW620 cells and SW620/L-OHP cells, and inhibition of autophagy can increase the efficacy of L-OHP. Ce6-PDT combined with L-OHP can further improve the tumor's therapeutic effect, and autophagy inhibition can improve the efficacy of combined therapy.