Research of mechanisms of swainsonine-induced apoptosis in the human gastric carcinoma cell line SGC-7901 / 中国临床药理学与治疗学

ABSTRACT

AIM: To investigate the effects and mechanisms of swainsonine-induced apoptosis on SGC-7901 cells. METHODES: After being treated with swainsonine, effective dose and median inhibition concentration (IC50) of swainsonine to SGC-7901 cells were examined by MTT assay. Cell cycle distribution and apoptotic rates were analyzed by flow cytometry. Expression of p53, c-myc and Bcl-2 were determined by immunocyto- chemical method, and the concentration of Ca2+ intra-cellular ([Ca2+]i ) was measured by the laser scanning confocal microscope (LSCM). RESULTS: Swainsonine inhibited cell growth of SGC-7901 in vitro, IC50 of 24 h was 0.84 μg·ml-l, and complete inhibition concentration of swainsonine was 6.2 μg·ml-l. Treated with swainsonine at the concentrations of 0.5, 1.5 and 4.5 μg·ml-l for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreased, and apoptotic trigger gene c-myc increased (P<0.05), as well as [Ca2+]i overloading, SGC-7901 cell was induced to apoptosis in the end. The percentage of S phase were 38.8%, 39.7% and 29.6%, respectively (20.0% in control group and 23.2% in 5-Fu group), the percentage of G2/M phase were 4.5%, 1.7% and 5.3%, respectively (5.5% in control group and 9.0% in 5-Fu group), and the percentage of G1/M phase was not altered. SGC-7901 cells were treated by swainsonine at the concentrations of 0.5, 1.5 and 4.5 μg·ml-l for 24 h. Compared with the control group, the percentage of S phase were increased and that of G2/M cells were decreased significantly in treatment groups (P<0.01). CONCLUSION: Swainsonine can inhibit the cell proliferation and induce apoptosis of SGC-7901 cells, the mechanisms of swainsonine-induced apoptosis may related with [Ca2+]i overloading and expression of apoptosis-related genes.