Effect of mithramycin on cell cycle and apoptosis of gastric cancer cells and its possible mechanism

HE Haolan; LI Qian; JIANG Han; WANG Xiao; LU Ming

doi:10.3969/j.issn.1009-0460.2019.02.008

Abstract：Objective To investigate the effect of mithramycin (MTM) on cell cycle and apoptosis of gastric cancer cells and its possible mechanism. Methods BGC-823, SGC-7901, MKN-28, AGS and normal gastric mucosa GES-1 cells were cultured in vitro. Real-time fluorescence quantitative analysis (QPCR) and Western blotting were used to detect the expression of SP1 mRNA and protein. BGC-823 cells were treated with 0, 25, 50 and 100 nmol/L MTM for 24 hours. The expression of SP1, p53 and p21 were detected by QPCR and Western blotting. Flow cytometry was used to detect the changes of cell cycle and apoptosis in BGC-823 cells treated with 50 nmol/L MTM. Results The expression of SP1 in BGC-823, SGC-7901, MKN-28 and AGS cell lines was 6. 12 ± 0. 15, 5. 42±0. 24, 3. 33±0. 21 and 3. 01±0. 12 by QPCR, which were significantly higher than those in GES-1 cell lines (P＜0. 05). Western blotting showed that the expression of SP1 protein was consistent with that of mRNA. When BGC-823 cells were treated with 0, 25, 50 and 100 nmol/L MTM, the expression of SP1 decreased gradually, while the expression of p53 and p21 increased gradually. Compared with 0 nmol/L MTM group, the expression of SP1 was the lowest and p53 was the highest in 50 nmol/L MTM group and the expression of p21 was the highest in 100 nmol/L MTM group (P＜0. 05). Flow cytometry showed that the G0/G1 ratio and apoptotic rate of BGC-823 cells in 50 nmol/L MTM group were (63. 71±2. 14) ％ and (24. 68± 1. 09) ％ respectively, which were significantly higher than those in 0 nmol/L MTM group. Conclusion Mithramycin can increase cell cycle arrest and induce apoptosis by decreasing SP1, increasing p53 and p21 expression.