Hua Suhang, Kong Xiangyu, Chen Binbin, Zhuang Wenxin, Sun Qian, Yang Wei, Liu Wenzhi, Zhang Yongxing
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China.
Department of Gastrointestinal Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China.
Curr Mol Pharmacol. 2018;11(4):316-325. doi: 10.2174/1874467211666180813095050.
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.
探讨洛铂单药及联合紫杉醇抑制人胃癌SGC-7901细胞增殖的机制。
处理后，采用MTT法评估细胞活力；通过流式细胞术评估细胞周期分布。采用蛋白质印迹法对细胞周期蛋白D1、E1、B1和细胞周期蛋白依赖性激酶2/4的蛋白水平进行定量分析。
洛铂和紫杉醇均呈浓度和时间依赖性抑制SGC-7901细胞生长，48小时的IC25值分别为1.97±0.17μg/ml和1.98±0.19 ng/ml。有趣的是，两种药物协同抑制SGC-7901细胞（联合指数[CI]<0.95）。洛铂不影响细胞周期蛋白D1和细胞周期蛋白依赖性激酶4的蛋白表达，而细胞周期蛋白E1和细胞周期蛋白依赖性激酶2的水平显著升高，细胞周期蛋白B1的量显著降低（p<0.05）。与对照组相比，洛铂处理后观察到更多的S期细胞（60.03±1.25 vs. 18.69±0.96%；p<0.05）。紫杉醇处理后，细胞周期蛋白D1和细胞周期蛋白依赖性激酶4的蛋白水平与对照值相似；同时，与对照值相比，细胞周期蛋白E1和细胞周期蛋白依赖性激酶2的蛋白量减少，细胞周期蛋白B1水平升高（p<0.05）。与对照值相比，紫杉醇处理后获得更多的G2/M期细胞（74.54±0.92 vs. 18.62±0.44%，p<0.05）。洛铂与紫杉醇联合使用不影响细胞周期蛋白D1和细胞周期蛋白依赖性激酶4的蛋白水平（p>0.05）；同时，与对照值相比，细胞周期蛋白E1和细胞周期蛋白依赖性激酶2的水平升高，细胞周期蛋白B1的量减少（p<0.05）。值得注意的是，联合处理后与对照值相比获得更多的S期（43.23±0.81 vs. 22.32±0.86%）和G2/M期（31.22±0.96 vs. 25.81±2.08%）细胞。
洛铂与紫杉醇协同抑制SGC-7901细胞。
