Inhibitory effects of disulfiram combined with paclitaxel on proliferation and invasion of esophageal cancer cells and their mechanism
Objective To investigate the inhibitory effects of disulfiram combined with paclitaxel on the proliferation and invasion of esophageal cancer cells and their mechanism.Methods The esophageal cancer cell lines TE-1 and TE-10 were treated with different concentrations of disulfiram(0,10,20,40 μmol/L),and the cell viability was measured by CCK-8 method to screen the optimal concentration of disulfiram.The intervention concentration of disulfiram was 20 μmol/L.TE-1 and TE-10 esophageal cancer cells were divided into the control group(normal culture without drugs),di-sulfiram group(20 μmol/L disulfiram),paclitaxel group(0.5 μmol/L paclitaxel),disulfiram + paclitaxel group(20 μmol/L disulfiram +0.5 μmol/L paclitaxel),respectively.MTT assay was used to observe the cell proliferation,flow cy-tometry was used to observe the apoptosis rate,Transwell assay was used to observe the cell invasion ability,RT-qPCR was used to detect the mRNA of α-tubulin,and Western blotting was used to detect the protein expression levels of α-tubulin and B-cell lymphoma-2(Bcl-2).Results The proliferation rates of TE-1 and TE-10 cells were in the following order:control group>disulfiram group>paclitaxel group>disulfiram + paclitaxel group,apoptosis rates of TE-1 and TE-10 cells were as follows:control group<disulfiram group<paclitaxel group<disulfiram + paclitaxel group,the number of trans-membrane TE-1 and TE-10 cells was as follows:control group>disulfiram group>paclitaxel group>disulfiram + paclitax-el group,the expression of α-tubulin mRNA in TE-1 cells was as follows:control group>disulfiram group>paclitaxel group>disulfiram + paclitaxel group,the expression of α-tubulin mRNA in TE-10 cells was in the following order:control group>disulfiram group>paclitaxel group,disulfiram + paclitaxel group,and the expression levels of α-tubulin and Bcl-2 protein in TE-1 and TE-10 cells were as follows:control group>disulfiram group>paclitaxel group>disulfiram + pacli-taxel group(all P<0.05).Conclusion Disulfiram combined with paclitaxel may enhance the inhibitory effects on the proliferation and invasion of esophageal cancer cells probably by down-regulating tubulin and promoting apoptosis.
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