Norcantharidin enhanced cisplatin sensitivity via YAP pathway in A549 cells / 中国药理学通报

ABSTRACT

Aim To investigate the effect of cotreat-ment norcantharidin (NCTD) and cisplatin (DDP) on the cisplatin sensitivity and proliferation in A549 cells, and whether YAP molecule involved in this process. Methods A549 cells were used as a model for inves-tigating the function of NCTD and DDP in this study. The expression of caspase-3,Annexin V,YAP,CTGF and Cyr61 were detected using RT-PCR and Western blot assay. The cell growth and proliferation were as-sessed by MTT and CCK-8 assay. Moreover, the tran-scriptional activity of YAP was detected by luciferase reporter gene assays. Results YAP was required for the cell growth and proliferation. NCTD,DDP and co-treatment of NCTD and DDP depressed cell viability, inhibited cell proliferation and promoted the sensitivity of cisplatin in A549 cells. Our results showed that the higher expressed oncogene YAP activated and promoted cell proliferation in lung cancer cells. Moreover, the high concentration of NCTD or DDP significantly re-duced cell proliferation, but cotreatment of NCTD and DDP in low concentration could significantly increase the cisplatin sensitivity via YAP pathway in A549 cells. Conclusions The cotreatment of NCTD and DDP in low concentration significantly reduces the transcriptional activity and protein level of YAP, then inhibits cell proliferation and thus increases the sensi-tivity of DDP in A549 cells.