Indomethacin sensitizes human lung cancer cells to DDP through autophagy activation in a mouse model

Abstract Background: Indomethacin is one of the non-steroidal anti-inflammatory drugs (NSAIDs) , and it was considered to have chemosensitization effects on many cancers, however, the mechanism of its effect on chemotherapy is still unclear. In this study, using human lung cancer SPC-A-1 cells, we examined the effects of indomethacin sensitize s human lung cancer cells to cisplatin (DDP). Methods: Human lung cancer SPC-A-1 cells were inoculated subcutaneously into BALB/c-nu/nu mice, and all the transplanted nude mice were divided into a control group, a DDP group and a indomethacin combined with DDP group , after daily treatment for 4 weeks a ll the mice were sacrificed by cervical dislocation. Immunohisto-chemical staining was employed to determine the expression of PCNA of lung tumor cell in the tumor tissues, western blot was used to detect the expression of autophagy related protein LC3-II and P62 What’s more, the formation of antophagosomes was observed through transmission electron microscope. Results: Compared with the control group and DDP group, we can find that tumor growth is very slow in indomethacin combined with DDP group , and the tumor weight decreased significantly in combined group. H&E staining reveal s that tumor cell necrosis is more obvious in combined group . The immunohistochemical staining results indicated that the expression of PCNA was much lower in combined group . than that in control and DDP group s.More importantly, western blot results show that the expression of LC3-II was significantly up-regulated in combined group than that in control group and DDP group ( P < 0.05 ) , and the expression of p62 protein was significantly down-regulated in combined group ( P < 0.05 ). Moreover, transmission electron microscope results show that compared with the control group and DDP group, the number of antophagosomes increased significantly in combined group. Conclusions : Our findings suggested that indomethacin can enhance the chemo s ensitivity of lung cancer cells to DDP, and the underlying mechanism maybe associated with the activation of autophagy.