Study On The Inhibitory Effects Of Dihydroartemisinin On The Proliferation And Metastasis Of Gastric Cancer Cell BGC-823

Part Ⅰ Study on the anti-growth effect of DHA and its potential mechanism in the gastric cancer cell line BGC-823Aim:Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has been shown to exhibit strong anticancer activity. In this study, we investigated the in vitro and in vivo influence of DHA on malignant phenotypes (proliferation, cell cycle, and apoptosis) of gastirc cancer BGC-823 cells and elucidated its potential mechanism.Methods:MTT assay was applied to detect the killing effect of DHA and 5-fluorouraci (5-FU) on BGC-823 cells. Cell cycle and apoptosis were analyzed using flow cytometry. The protein levles of Bax, Bcl-2 and Caspase-3 were determined by Western blotting analysis, and the Caspase-3 activity was also checked using spectrophotometry. A BGC-823 xenograft tumor model was estabelised to evalutate the in vivo anti-tumor effect of DHA.Results:DHA treatment at different concentrations (10μmol/L,20μmol/L, and 40μmol/L) could induce a significant proliferation inhibition in gastric cancer cell BGC-823 compared with untreated control cells. DHA increased the cytotoxic effect of 5-FU on BGC-823, and decreased its IC50 from 3.04 μg/mL to 1.42 μg/mL. The cell population of G2/M phase and apoptosis rate in BGC-823 cells treated with varied concentrations of DHA (10μmol/L,20μmol/L, and 40μmol/L) were increased significantly compared with untreated control (P<0.05). Decreased Bcl-2 and increased Bax protein expression were observed in BGC-823 cells treated with DHA, and increased expression and activity of caspase-3 were also observed in DHA-treated BGC-823 cells. In addition, DHA significantly inhibited the growth and induced apoptosis in a BGC-823 xenograft tumor model.Conclusion:DHA could inhibit the gastric cancer growth, arrest the cell cycle at G2/M phase and induce apoptosis. In addition, DHA could increase the cytotoxic effect of 5-FU on gastric cancer. The inhibitory effect of DHA on gastric cancer was mediated by decreasing Bcl-2 expression and increasing Bax expression.Part Ⅱ Study on the influence of DHA on the invasion and metastasis and its potential mechanism in the BGC-823 gastric cancer cellAim:To investigate the influence of DHA on the migration, adhesion and invasion of gastric cancer BGC-823 cells and to elucidate its potential mechanism.Methods:Transwell assay was used to evaluate the effects of DHA on the migration and invasion BGC-823 cells, and cell adhesion assay was applied to check the influence of DHA on the in vitro adhesion of BGC-823 cells. The mRNA and protein expression of VEGF were detected using real time quantitative RT-PCR and ELISA, respectively. A mouse model of pulmonary metastasis was established using caudal vein injection of BGC-823 cells, and the in vivo effect of DHA on the cancer metastasis was studied using the intragastric administration of DHA.Results:Compared to the untreated control, DHA treatment at different concentrations (20μmol/L and 40μmol/L) could significantly inhibit the migration, adhesion and invasion of BGC-823 cells. Both the mRNA and protein expression of VEGF was significant decreased in DHA-treated gastric cancer cells compared with the control cells. DHA therapy significantly reduced the number of lung metastasis sites (P<0.01).Conclusion:DHA could inhibit the metastasis ability of gastric cancer, which may be mediated by decreasing VEGF expression.