Inhibition of miR-22 enhanced the efficacy of icotinib plus pemetrexed in a rat model of non-small cell lung cancer

Objective(s): To investigate the role of miR-22 in the efficacy of combined icotinib (BPI-2009H) and pemetrexed (LY-231514) on tumor growth and apoptosis in rats with non-small cell lung cancer (NSCLC). Materials and Methods: Rats were injected with HCC827 cells, which were transfected with anti-miR-22, followed by the treatment of BPI-2009H and/or LY-231514. MTT assay was used to detect the inhibition rate of HCC827 cells. qRT-PCR was performed to examine miR-22 expression in HCC827 cells and lung tumor tissues. Moreover, immunohistochemistry and Western blotting were performed to detect the relatedmolecule expressions, while TUNEL staining was used to observe cell apoptosis of lung tumor tissues. Results: MiR-22 expression was decreased in HCC827 cells after the treatment of BPI-2009H or LY- 231514 in a dose-dependent manner. Both BPI-2009H and LY-231514 increased the inhibition rate of HCC827 cells, which was enhanced by anti-miR-22 with decreased IC50 values. Furthermore, the decreased expression of miR-22 was found after the treatment of BPI-2009H or/and LY-231514 in lung tumor tissues. In addition, the expressions of PCNA, Ki67, and Bcl-2 were reduced, but Bax and Caspase-3 were increased in treated rats, typically in those rats treated with the combination of antimiR- 22, BPI-2009H, and LY-231514. Conclusion: Inhibition of miR-22 could enhance the efficacy of icotinib combined with pemetrexed in rats with NSCLC, providing a new perspective for NSCLC therapy.