Abstract: ponding Author E-mail: jxgzguosj Abstract: Objective To investigate the effect of targeting silenced aquaporin 4 (AQP4) gene on the chemotherapy sensitivity of non-small cell lung cancer (NSDCLC) and its mechanism. Methods The qRT-PCR method and Western bolt assay were used to detect the expression of AQP4 in A549 and A549/DDP cell lines (human cisplatin-resistant NSDCLC cell line). The siRNA-1 and siRNA-2 targeting AQP4 were designed. AQP4 expression was blocked by the siRNA in A549/DDP cells. The optimal siRNA was screened and transfected into A549/DDP cells. siRNA-NC and blank cells were set up as controls. The proliferation and half inhibitory concentration (IC50) of A549/DDP cells were detected by CCK8 method. The apoptosis of U251 cells was detected by AnnexinV- FITC/PI double marker flow cytometry. The expressions of P53 and Bcl- 2 were detected by Western blot assay. Results The expressions of AQP4 mRNA and protein were significantly increased in A549 /DDP cells compared with A549 cells. After silencing AQP4 expression, the proliferation was inhibited and the apoptosis rate was significantly increased in A549 / DDP cells. Silencing AQP4 expression significantly increased the sensitivity to cisplatin in lung cancer cells. AQP4 knockdown could also up-regulate the expression of P53, and down regulate the expression of Bcl-2. Conclusion The selective targeting of the AQP4 expression can increase the sensitivity of NSDCLC cells to chemotherapeutic drugs.

Key words: NSCLC, target regulating, durg-resistance, AQP4, RNA interference