P-glycoprotein, which is the MDR1 gene product, confers cancer cell resistance to a broad range of GSI-IX clinical trial chemotherapeutics. Zhu, et al demonstrate for the first time the roles of miRNAs in the regulation of drug resistance mediated by MDR1/P-glycoprotein, and suggest the potential for targeting miR-27a and miR-451 as a therapeutic strategy for modulating MDR in cancer cells [13]. Olga and his colleagues reported that the enforced increase of miR-451 levels in the MCF-7/DOX mTOR inhibitor cells down-regulates expression of mdr1 and increases sensitivity of the MCF-7-resistant cancer cells to

DOX [14]. All these data provide a strong rationale for the development of miRNA-based therapeutic strategies aiming to overcome chemoresistance of tumor cells. However, whether the expression of miR-451 can affect the sensitivity of lung cancer cells to DDP is still unclear. In the present study, we found that the upregulation of miR-451 could significantly ATM/ATR targets inhibit growth and colony formation of NSCLC cell line (A549). Upregulation of miR-451 could also enhance caspase-3-dependent apoptosis of A549 cells by

inactivating the Akt signalling pathway which induced the reverse of Bcl-2/Bax ratio. Furthermore, upregulation of miR-451 could significantly increase the in vitro and in vivo sensitivity of A549 cells to DDP. To the best of our knowledge, we provided the first insight into the roles and possible mechanisms of miR-451 upregulation in chemosensitivity of A549 cells to DDP. These data suggest that appropriate combination of DDP application with miR-451 regulation might be a potential

approach to NSCLC therapy. For higher-dose DDP would produce potentially serious toxic effects such as nephro- and ototoxicity would be increased, combination of DDP application with miR-451 upregulation for the treatment of NSCLC would contribute to lower-dose DDP administration and result in a reduction of DDP toxic side-effects. Although inhibition of Akt signal pathway has been reported to be able to improve chemotherapeutic effect of human tumor cells, whether upregulation of miR-451 enhance DDP chemosensitivity of A549 cells by inactivating the Akt signal pathway needs to be further Chlormezanone elucidated. Moreover, only A549 cell line has been used in this study, further researches should be conducted on other cell lines to testify our experimental data. In conclusion, upregulation of miR-451 could increase the sensitivity of A549 cells to DDP both in vitro and in vivo, suggesting that appropriate combination of DDP application with miR-451 upregulation might be a potential strategy for the treatment of human NSCLC in future. Acknowledgements This work was supported by grants from the National Natural Science Foundation of China (No. 30973477), the Natural Science Foundation of Jiangsu province (No.