The Effect Of Harmine On COX-2Expression And Its Biological Effect In Gastric Cancer

BackgroudCyclooxygenase-2(COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. Harmine is reported as a promising drug candidate for cancer therapy, however, effects and action mechanism of harmine on the human gastric cancer cells remain unclear. This study evaluated the anti-tumor effects of harmine on human gastric cancer both in vitro and in vivo in order to further demonstrate its possible anti-tumor mechanism.ObjectiveTo investigate the effect of harmine on COX-2expression and its biological effect in gastric cancer.MethodsBGC-823and SGC-7901cells were seeded into96-well microplate and incubated overnight. After treatment with different concentrations of harmine for24,48and72h, the cell proliferation was determined using MTT colorimetric assay. Apoptosis was measured by DAPI staining and flow cytometry analysis. The wound-healing and transwell invasion assays were performed to evaluate the effects of harmine on the migration and invasion of gastric cancer cells. The expressions of COX-2, matrix metalloproteinase-2(MMP-2), proliferating cell nuclear antigen (PCNA), Bcl-2and Bax were detected by western blot analysis. To further explore the effect of harmine on tumor growth in vivo, a gastric xenograft tumor model was established.ResultsHarmine could significantly inhibited cellular-proliferation, migration, invasion and induced apoptosis in vitro, as well as inhibited tumor growth in vivo. In addition, harmine effectively inhibited the expressions of COX-2, MMP-2, PCNA and Bcl-2as well as increased Bax expression in gastric cancer cells.ConclusionThese results collectively indicate that harmine induces apoptosis and inhibits proliferation, migration and invasion of human gastric cancer cells may be mediated by down-regulation of COX-2expression.