Mechanism of Synergistic Effect of YM-155 on Cisplantin-Induced Cytotoxicity Against NSCLC

OBJECTIVE To explore the adjuvant effect of YM-155 on cisplatin-based chemotherapy in non-small cell lung cancer(NSCLC). METHODS MTT assay was performed to evaluate the cytotoxicity of YM-155 and cisplatin to A549 cells. Western blot analysis was conducted to detect the expression of survivin, cytochrome C, apoptosis inducing factor, caspase-9 and caspase-3 in A549 cells. Flow cytometry analysis was performed to detect the mitochondrial membrane potential and apoptosis of A549. RESULTS YM-155 conled enhance the anti-lung cancer activity of cisplation, and decreased the IC₅₀ of cisplatin to A549. YM-155 inhibited the expression of survivin in A549. Mitochondrial membrane potential of A549 in cisplatin+YM-155 group was significantly lower than that in the cisplatin single treatment group. Apoptotic rate, release of cytochrome C and apoptosis inducing factor, activation of caspase-9 and caspase-3 in the cisplatin+YM-155 group was obviously higher than these in the cisplatin single treatment group. On the other hand, relative cell viability and mitochondrial membrane potential of A549 in cisplatin+YM-155+survivin plasmid group was significantly higher than those in the cisplatin+YM-155 group. However, apoptotic rate, release of cytochrome C and apoptosis inducing factor, activation of caspase-9 and caspase-3 in the cisplatin+YM-155+survivin plasmid group was obviously lower than those in the cisplatin+YM-155 group. CONCLUSION YM-155 enhances the cisplatin-induced mitochondrial apoptosis in NSCLC cells through inhibition of survivin.