Apatinib Suppresses Biological Activities of Non-Small-Cell Lung Carcinoma(A549) Cells by Depressing miRNA-21 via the PTEN/PI3K/AKT Pathway

Abstract

Objective: To explain the anti-tumour effects of apatinib via the regulation of miRNA-21 in the PTEN/PI3K/AKT pathway. Methods: Measuring pathology, miRNA-21 and PTEN expression by H&E staining, in-situ hybridisation and immunohistochemistry in non-small-cell lung carcinoma (NSCLC). For the experiment, A549 cells were divided into four groups: apatinib, apatinib+blank, apatinib+miRNA and negative control. Cell proliferation, apoptosis, cell cycle, invasion and migration were assessed using the MTT, flow cytometry, transwell migration and wound-healing assays. Relative expressions of PTEN, PI3K, AKT, P21, MMP-2 and MMP-9 were evaluated using western blotting. Results: miRNA-21 and PTEN protein expressions of NSCLC tissues were found to significantly differ from those of adjacent normal tissues (P < 0.001). Compared with the control group, the cell apoptosis rate was significantly suppressed with increasing cell apoptosis in the G1 phase in the apatinib group (P < 0.001); the invasion A549 cell number and wound-healing rate were significantly depressed in the apatinib group compared with the control group (P < 0.001). However, A549 cell biological activities were significantly recovered with miRNA-21 transfection in the apatinib+miRNA group (P < 0.001). Western blotting revealed that PTEN and P21 expression in the apatinib group were significantly upregulated and that PI3K, AKT, MMP-2 and MMP-9 expression were significantly downregulated compared with the control (P < 0.001). miRNA-21 transfection led to significant suppression of PTEN and P21 expression and significant stimulation of PI3K, AKT, MMP-2 and MMP-9 expression (P < 0.001). Conclusion: Apatinib was proven to exhibit anti-tumour effects to NSCLC by regulating miRNA-21 via the PTEN/PI3K/AKT pathway.