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. 2015 Aug 1;8(8):9072-80.
eCollection 2015.

Docetaxel inhibits the proliferation of non-small-cell lung cancer cells via upregulation of microRNA-7 expression

Xigan He  1 , Chunxia Li  1 , Xiaoyan Wu  1 , Guotao Yang  1
Affiliations

Docetaxel inhibits the proliferation of non-small-cell lung cancer cells via upregulation of microRNA-7 expression

Xigan He et al. Int J Clin Exp Pathol. .

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide and about 85% of these are non-small cell lung cancer (NSCLC). Several new chemotherapeutic agents have recently shown encouraging activity in NSCLC, especially docetaxel. MiRNAs (MicroRNAs) are closely related to cancer development. We studied miRNAs in NSCLC cell lines to identify those that can regulate and predict the effectiveness of docetaxel on NSCLC. CCK8, Annexin and V-FITC assays were carried out to evaluate the inhibitory effect of docetaxel on NSCLC cell lines A549 and H460, and qRT-PCR was used to detect and compare six miRNAs expression levels in the two cells with docetaxel or not. Knockdown of miR-7 by RNA interference and overexpression of miR-7 were taken to evaluate the effect of miR-7 on docetaxel effectiveness. Western blotting was used to evaluate the effect of miR-7 on Bcl2 in A549 and H460 cells. Docetaxel induced non-small cell lung cancer cell apoptosis and suppressed cell proliferation in vitro. MiR-7 expression levels were increased by docetaxel in the two cell lines. MiR-7 overexpression improved anti-proliferative and pro-apoptotic effects of docetaxel on the NSCLC cells and that miR-7 down-regulation decreased those effects. Moreover, subsequent experiments showed that BCL-2 was downregulated by miR-7 at both transcriptional and translational levels. This study further extends the biological role of miR-7 in NSCLC A549 and H460 cells and identifies BCL-2 as a novel target possibly involved in miR-7-mediated growth suppression and apoptosis induction of NSCLC cells.

Keywords: docetaxel; miR-7; miRNA; non-small cell lung cancer.

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Figures

Figure 1
Figure 1
Docetaxel suppressed cell proliferation and induced apoptosis of A549 cells and H460 cells. Cells were treated with different doses of docetaxel (0, 0.025, 0.05, 0.1, 0.2, 0.4 and 1.0 μM) for 48 h. A. The cell viability was determined using a Cell Counting kit-8 assay. B. Apoptosis of A549 and H460 cells were detected by Annexin V/PI assay following 72-h exposure to docetaxel. Results are shown as mean ± SEM. Data is representative of three independent experiments.
Figure 2
Figure 2
Expression of miR-7 is upregulated by docetaxel in NSCLC cell lines. Six miRNAs expression in NSCLC cell lines were measured by quantitative polymerase chain reaction (*P<0.05, **P<0.01).
Figure 3
Figure 3
Overexpression of miR-7 in NSCLC cell lines. A. MiR-7 expression in A549 and H460 cells, following transfection with miR-7 or miR-NC, was determined by quantitative polymerase chain reaction. B. A549 and H460 cells were transfected either with miR-7 or miR-NC for 24 hours. BCL-2 mRNA levels were measured by real time RT-PCR, normalized with endogenous GAPDH and expressed as fold change compared with control. C. BCL-2 protein levels were examined by Western blot using GAPDH as a loading control. Results are shown as mean ± SEM. Data are representative of three independent experiments (*P<0.05, ***P<0.01).
Figure 4
Figure 4
Knockdown of endogenous miR-7 expression enhances the protein expression of Bcl-2 in A549 and H460 cells treated with docetaxel. A. MiR-7 expression in A549 and H460 cells following transfection with the miR-7 or miR-7 inhibitor was detected by quantitative polymerase chain reaction. B. Cell viability of A549 and H460 cells was evaluated by Cell Counting kit-8 (CCK-8) assay following transfection with the miR-7 inhibitor and docetaxel combined treatment. C. Bcl-2 protein level was examined by Western blotting using GAPDH as a loading control. D. Apoptosis of A549 and H460 cells were determined by Annexin V/PI assays 48 h after transfection with the miR-7 inhibitor and docetaxel combined treatment (*P<0.05, **P<0.01).
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