Cooperative inhibitory effect of sinomenine combined with5-fluorouracil on esophageal carcinoma

AIM:To investigate the inhibitory effects of sinomenine(SIN)combined with 5-fluorouracil(5-FU)on esophageal carcinoma in vitro and in vivo.METHODS:Esophageal carcinoma(Eca-109)cells were cultured in DMEM.The single or combined growth inhibition effects of SIN and 5-FU on the Eca-109 cells were examined by measuring the absorbance of CCK-8dye in living cells.Hoechst 33258 staining and an Annexin V/PI apoptosis kit were used to detect the percentage of cells undergoing apoptosis.Western blotting was used to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis.SIN at 25mg/kg and 5-FU at 12 mg/kg every 3 d,either combined or alone,was injected into nude mice and tumor growth inhibition and side effects of the drug treatment were observed.RESULTS:SIN and 5-FU,both in combination and individually,significantly inhibited the proliferation of Eca-109 cells and induced obvious apoptosis.Furthermore,the combined effects were greater than those of the individual agents(P<0.05).Annexin V/PI staining and Hoechst 33258 staining both indicated that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone were significantly different from the control(P<0.05).The up-regulation of Bax and downregulation of Bcl-2 showed that the essential mechanism of apoptosis induced by SIN and 5-FU occurs via the mitochondrial pathway.SIN and 5-FU alone significantly inhibited the growth of tumor xenografts in vivo,and the combined inhibition rate was even higher(P<0.05).During the course of chemotherapy,no obvious side effects were observed in the liver or kidneys.CONCLUSION:The combined effects of SIN and 5-FU on esophageal carcinoma were superior to those of the individual compounds,and the drug combination did not increase the side effects of chemotherapy.