The role of emodin on cisplatin resistance reversal of lung adenocarcinoma A549/DDP cell.

Abstract

Exploring drugs that reverse drug resistance and increase the sensitivity of chemotherapy drugs could significantly improve treatment effect of cancer. Our study explored the reversal effect and possible molecular mechanisms of emodin on cisplatin resistance in A549/DDP cells. The IC50 and resistance index of cells were determined by Cell Counting Kit-8 assay. The ability of cell proliferation was evaluated by wound healing assay. Transwell assay was used to detect cell invasion and migration. Apoptosis induction rate was determined by flow cytometry assay and 4',6- diamidino- 2-phenylindole staining. Intracellular concentration was determined by HPLC. Western blot analysis was applied to determine expressions of nuclear factor kappa beta (NF-κB) and its downstream proteins. In this study, we found that the growth inhibitory effect of cisplatin was significantly enhanced by emodin in A549/DDP cells. The combined use of emodin with DDP can effectively promote lung cancer cells apoptosis and inhibit cell migration and invasion. Further investigation indicated that reinforcement effect of emodin and DDP may be associated with inhibition of NF-κB pathway and drug efflux-related proteins such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and Glutathione S-transferase (GST). The key role of NF-κB was further confirmed by the application of NF-κB inhibitor Ammonium pyrrolidinedithiocarbamate. The intervention of both can significantly increase A549/DDP cell apoptosis and inhibit DDP-induced upregulation of P-gp, MRP and GST. Emodin reverses the cisplatin resistance of tumor cells by down-regulating expression of P-gp, MRP and GST, increasing the intracellular accumulation in A549/DDP cells, and the effect may be associated with the NF-κB pathways.