Anticancer Mechanism of Lobaplatin as Monotherapy and in Combination with Paclitaxel in Human Gastric Cancer

To explore the mechanism by which lobaplatin, as monotherapy and in combination with paclitaxel, inhibits the proliferation of human gastric cancer SGC-7901 cells.

After treatment, the MTT assay was used to assess cell viability; cell cycle distribution was evaluated flow-cytometrically. Western blot was used to quantitate cyclin D1, E1, B1, and Cdk2/4 protein levels.

Lobaplatin and paclitaxel inhibited SGC-7901 cell growth in a concentration and timedependent manner, with IC25 values at 48h of 1.97±0.17µg/ml and 1.98±0.19 ng/ml, respectively. Interestingly, both drugs synergistically inhibited SGC-7901 cells (combination index [CI]<0.95). Lobaplatin did not affect cyclin D1 and CDK4 protein expression, while cyclin E1 and CDK2 levels were significantly increased, with cyclin B1 amounts markedly decreased (p<0.05). More S phase cells were observed after lobaplatin treatment compared with controls (60.03±1.25 vs. 18.69±0.96%; p<0.05). After treatment with paclitaxel, cyclin D1 and CDK4 protein levels were similar to control values; meanwhile, cylinE1 and CDK2 protein amounts were reduced, with increased cyclin B1 levels, compared with control values (p<0.05). More G2/M cells were obtained after treatment with paclitaxel compared with control values (74.54±0.92 vs. 18.62±0.44% (p<0.05). Lobaplatin and paclitaxel combination did not affect cyclin D1 and CDK4 protein levels (p>0.05); meanwhile, cyclin E1 and CDK2 levels were increased, with reduced cyclin B1 amounts, compared with control values (p<0.05). Notably, more S (43.23±0.81 vs. 22.32±0.86%) and G2/M (31.22±0.96 vs. 25.81±2.08%) phase cells were obtained after combined treatment compared with control values.

Lobaplatin and paclitaxel synergistically inhibit SGC-7901 cells.