Abstract:

Objective To investigate the inhibitory effect of melatonin in conjunction with 5⁃fluorouracil and its molecular mechanism in esophageal cancer. Methods Human esophageal carcinoma EC⁃9706 and EC⁃109 cells were treated with MLT and 5⁃FU at different concentrations.The effects of MLT on the chemotherapy sensitivi⁃ ty of 5⁃FU were investigated by detecting cell activity，invasion，migration，apoptosis and protein expression，and the possible mechanism was further explored.The synergistic antitumor effect of MLT and 5⁃FU was investigated by tumor⁃bearing experiment. Results MLT inhibited the activity of EC⁃9706 and EC⁃109 cells in a dose⁃dependent manner. Compared with blank controls，melatonin reduced the invasion and migration of EC ⁃ 9706 and EC ⁃ 109 cells（P < 0.01），but increased the apoptosis rate（P < 0.01）. Compared with MLT and5⁃FU alone group，the combinational use of melatonin and 5⁃FU significantly reduced the proliferation，invasion，migration and apoptosis of esophageal carcinoma cells（P < 0.01）. Meanwhile，compared with MLT and5⁃FU alone，the combinational use of melatonin and 5⁃FU significantly reduced EZH2 expression，and overexpression of EZH2 reversed the effects of MLT and 5⁃FU on EC⁃9706 cells（P < 0.01）. In addition，MLT and 5⁃FU combined administration significantly inhibited the growth of esophageal cancer in nude mice compared with 5⁃FU alone（P < 0.01）. Conclusion The combinational use of melatonin and 5⁃FU promotes apoptosis by inhibiting the expression of EZH2，thus improving 

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