Effect of pemetrexed combined with oxaliplatin on the growth of human gastric cancer cell BGC-823

Objective: To investigate the growth inhibition effects of pemetrexed and oxaliplatin on human gastric cancer cell line BGC-823 in vitro, and to explore the possible mechanism.  Methods: The BGC-823 cells were treated with different concentrations of pemetrexed or oxaliplatin alone or in combination. The growth inhibition rate of BGC-823 cells was detected by MTT method, and the change of cell cycle distribution was analyzed by flow cytometry (FCM). The expressions levels of proliferating cell nuclear antigen (PCNA) and cell cycle D1 (cyclin D1) proteins in BGC-823 cells were examined by Western blotting.  Results: The growth of BGC-823 cells was inhibited by pemetrexed or oxaliplatin in a dose- and time-dependent manner (P＜0.05). The percentage of cells in G1 phase was increased while which in S phase was decreased by the treatment of pemetrexed or oxaliplatin. The expression levels of PCNA and cyclin D1 proteins were significantly decreased, and the combination regimen of pemetrexed and oxaliplatin exerted a synergistic effect. The growth inhibition rate of BGC-823 cells treated with pemetrexed (80 μg/mL) for 24 h followed by oxaliplatin (40 μg/mL) for 24 h was significantly decreased as compared with those of the cells treated with pemetrexed (80 μg/mL) combined with oxaliplatin (40 μg/mL) at the same time or treated with oxaliplatin (40 μg/mL) for 24 h followed by pemetrexed (80 μg/mL) for 24 h (P＜0.05).  Conclusion: Pemetrexed and oxaliplatin can both inhibit the proliferation of gastric cancer BGC-823 cells and arrest the cells at G1 phase. The sequential regimen of pemetrexed followed by oxaliplatin may have the strongest growth-inhibitory effect on gastric cancer cells among different doublet regimens. DOI:10.3781/j.issn.1000-7431.2011.12.003