Open AccessDCLAK11 treatment induces apoptosis in non‐small cell lung cancer cells by inhibiting the mitochondrial apoptosis pathway
Author(s) -
Guo Xiaobin,
Liu Hongchun,
Ding Jian
Publication year - 2019
Publication title -
precision radiation oncology
Language(s) - English
Resource type - Journals
ISSN - 2398-7324
DOI - 10.1002/pro6.1073
Subject(s) - apoptosis , annexin , microbiology and biotechnology , viability assay , pi , cell growth , cell , bcl xl , blot , western blot , chemistry , biology , programmed cell death , cancer research , biochemistry , gene
Objective DCLAK11 is a novel small molecule tyrosine kinase inhibitor with remarkable effects on cell proliferation and apoptosis in non‐small cell lung cancer cells. Therefore, it is necessary to determine the molecular mechanisms of action of this compound. In this study, we investigated the antitumor effect that DCLAK11 exerts through inhibition of the mitochondrial apoptosis pathway. Methods Cell viability was assessed using the Cell Counting Kit‐8 assay, and apoptosis was measured by an Annexin V‐PI assay. The mitochondrial transmembrane potential was examined using JC‐1 dye. Alterations in expression of the Bcl‐2 family proteins Bcl‐xL, Bax, Bid, Bim, Bad, and cleaved Caspase‐9 were detected by western blotting. Results DCLAK11 inhibited the proliferation of non‐small cell lung cancer cells HCC827 (IC 50 = 10 nmol/L) and HCC4006 (IC 50 = 20 nmol/L) in a dose‐dependent manner. The Annexin V‐PI assay results showed that DCLAK11 also significantly promoted apoptosis in both HCC827 and HCC4006 cells in a dose‐dependent manner ( F = 29.990, P < 0.00; F = 46.439, P < 0.001, respectively). The JC‐1 assay results showed that the proportion of depolarized cells significantly increased with increasing concentrations of DCLAK11 when compared with that in the control HCC827 and HCC4006 cells ( F = 63.910, P < 0.001; F = 11.831, P = 0.001, respectively). Western blot results showed that DCLAK11 caused a decrease in the expression level of Bcl‐xL and an increase in the expression of Bid, Bim, Bad, Bax, and cleaved caspase‐9 in a dose‐dependent manner. Furthermore, the proportion of Bcl‐xL/Bax decreased with increasing concentrations of DCLAK11 in HCC827 and HCC4006 cells. Conclusion We confirmed that DCLAK11 exerts an antitumor effect by inhibiting the mitochondrial apoptosis pathway.