The Therapy Effect Of Cisplatin In Combination With PD098059 On Gastric Cancer

ObjectiveTo investigate the antitumor roles of PD098059 and cisplatin on gastric cancer cells MGC803. To explore if PD098059 may increase the antitumor effect of cisplatin, and to study the change of intracellar Ca²⁺ level in the process.MethodsGastric cancer cells were treated with PD098059 (50umol/L), cisplatin (2ug/ml), or PD098059 in combination with cisplatin for 24 hour. The growth and proliferation of gastric cells were analyzed with MTT assay. Flow cytometric analysis, acridine orange fluorescent staining method and transmission electron microscopy were used to detect the apoptosis of the gastric cancer cells. Fluo-3/am fluorecin load technique determined the level of intracellular Ca²⁺ in the progress.ResultsThe inhibitory rates of the cells treated by PD098059, cisplatin and combination of two agents were 1.20±0.76, 17.25±1.23%, and 31.8±0.98% respectively. The inhibitory rate of the gastric cells treated with cisplatin combined with PD098059 was significantly greater than those of the cells treated by the two agents alone (both P < 0. 01). The apoptosis rates of the cells treated by PD098059, cisplatin and combination of two agents were 1.36%, 8.32%, 5.64% respectively, all significantly higher than that in the control group (0.20%, all P < 0. 01). The apoptosis rate of the gastric cells treated by cisplatin combined with PD098059 was significantly greater than those of the cells treated by the two agents alone (both P < 0. 01). Treated by cisplatin and combination of two agents, chromatin condensation and nuclear fragmentation were seen under fluorescence microscope in cells treated with acridine orange fluorescent staining method. The apoptosis cells were observed under transmission electron microscopy. An increase Ca²⁺ level in cytoplasm and a decrease Ca²⁺ level in cell nucleus were observed in the process.ConclusionCotreatment with cisplatin and PD098059 have synergistic anticancer role. The change of intracellular Ca²⁺ correlated with the therapic progress of cisplatin in combination with PD098059 on gastric cancer cells.