Toxic Effect and the Underlying Mechanism of Methyl-cantharidimide on human gastric cancer cells

• 1、School of Public Health, Medical College of Soochow University, Soochow 215123

Abstract： [Object] Methyl-Cantharidimide (MCA) is a derivative of cantharidin which has potential anticancer activity. This study investigates the cytotoxic effects of MCA on human gastric cancer cells. Human gastric cancer cells NCI-N87 and MKN-45, and normal human gastric epithelium immortalized cells GES-1 were treated with a series of concentrations of MCA, the proliferation rates of these cells was examined using CCK-8 assay. Cell cycle and cell apoptosis were determined using Flow Cytometry. Furthermore, Western blot was used to evaluate biomarkers associated with cell cycle and apoptosis. [Results] Methylcantharidin inhibited cell proliferation in human gastric cancer cells NCI-N87 and MKN-45 in a dose- and time-dependent manner; Compared with the control group, MCA exposure arrested NCI-N87 cells in S phase cell cycle and arrested MKN -45 cells in G-1 phase cell cycle (P <0.05); Compared with the control group, MCA significantly increased the apoptosis rate of human gastric cancer cells NCI-N87 and MKN-45 (P <0.05); compared with the control group, MCA significantly reduced the expression levels of survivin protein and NF-κB protein in gastric cancer cells NCI-N87 (P <0.05).[Conclusion] These results suggest that MCA has cytotoxic effect on NCI-N87 and MKN -45 cells. Its mechanism of action is by inducing cell cycle arrest and promoting cell apoptosis through inhibiting survivin and NF-κB. MCA could be developed into a novel drug for the treatment of human gastric carcinoma.

Keywords： Methyl-cantharidimide Apoptosis Cell cycle Survivin gene NF-κB gene Gastric cancer cells