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. 2020 Mar;23(3):329-336.
doi: 10.22038/IJBMS.2019.39291.9320.

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

Jing Zhang  1 , Zhi-Qiang Xue  1 , Bin Wang  1 , Jia-Xin Wen  1 , Yun-Xi Wang  1
Affiliations

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

Jing Zhang et al. Iran J Basic Med Sci. 2020 Mar.

Abstract

Objectives: 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 related-molecule 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 anti-miR-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.

Keywords: Carcinoma; Human; Icotinib; MIRN22 microRNA; Non-Small-Cell Lung; Pemetrexed.

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Figures

Figure 1
Figure 1
BPI-2009H and LY-231514 increased the inhibition rate of HCC827 cells, which was enhanced by anti-miR-22
Figure 2
Figure 2
General information of rats
Figure 3
Figure 3
qRT-PCR was used to detect the expression of miR-22 in lung tumor tissues of rat
Figure 4.
Figure 4.
The expression of PCNA and Ki67 in lung tumor tissues of rats in each group detected by immunohistochemistry staining
Figure 5
Figure 5
Protein expressions of PCNA and Ki-67 in lung tumor tissues of rats in each group by Western blotting
Figure 6.
Figure 6.
Cell apoptosis in lung tumor tissues of rats in each group
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