ABSTRACT
Objective: To investigate the effect of elemene on the drug resistance of cisplatin (DDP)-resistant human lung adenocarcinoma A549/DDP cells, and its possible mechanism. Methods: The growth inhibition of A549/DDP cells treated with elemene alone or combined with different concentrations of DDP was detected by MTT assay. The morphological changes of apoptosis of A549/DDP cells treated with different concentrations of elemene (20 and 40 μg/mL) for 24 h were observed by Hoechst 33342 staing under fluorescence a microscope. The apoptosis rate of A549/DDP cells treated with different concentrations of elemene (20 and 40 μg/mL) after 24 h were detected by FCM (flow cytometry). The expressions of cytochrome C, pro-caspase-3, caspase-3 and the Bcl-2 family proteins were measured by Western blotting analysis. Results: MTT result showed that different concentrations elemene could inhibit the proliferation of A549/DDP cells in a time- and dose- dependent manner. Intriguingly, elemene plus DDP enhanced the sensitivity of A549/DDP cells to DDP and reversed the resistance of A549/DDP cells. Elemene was also a strong inducer of apoptosis in this model system, and a synergistic effect on induction of cell death was observed when the tumor cells were treated with both agents. The result showed that elemene could enhance A549/DDP cell apoptosis. Furthermore, the combination of elemene and DDP also enhanced the protein expressions of cytochrome C, caspase-3 and Bad, and reduced the protein levels of Bcl-2 and pro-caspase-3 in the A549/DDP cells. Conclusion: The reversal of the multi-drug resistance of A549/DDP cell line by elemene may result from its effect on induction of apoptosis. Elemene treatment can impaire mitochondrial membrane, release cytochrome C into cytoplasm, activate caspase-3,up-regulate pro-apoptotic protein Bad and down-regulate anti-apoptotic protein Bcl-2, and finally caused apoptosis. Copyright © 2013 by TUMOR.