Apatinib has anti-tumor effects and induces autophagy in lung cancer cells with high expression of VEGFR-۲

Objective(s): This study investigated the inhibitory effect of apatinib on lung cancer cells with high expression of vascular endothelial growth factor-۲ (VEGFR-۲) and on inducing cellular autophagy and drug resistance. Materials and Methods: The expression of VEGFR-۲ was detected using western blotting and RT-PCR. Cell proliferation was measured using the CCK۸ and colony formation assays. The cell apoptosis rate was determined using flow cytometry and tunnel assay. Cellular autophagy was detected by measuring the expression of LC۳-II using Western blotting and cellular immunofluorescence. The inhibitory effect of apatinib on lung cancer cells and transplanted tumors was observed after treatment with the autophagy inhibitor chloroquine. Results: Apatinib dose-dependently inhibited the proliferation of H۱۹۷۵ and H۴۴۶ cells; it induced apoptosis via the PARP and caspase ۳ pathways in H۱۹۷۵ and H۴۴۶ cells and effectively inhibited the growth of transplanted tumors. Apatinib induced autophagy in a dose-dependent manner in H۱۹۷۵ and H۴۴۶ cells. The inhibitory effect of apatinib on cells and the promotion of apoptosis were significantly enhanced after treatment with chloroquine. Immunohistochemistry showed that combining apatinib with chloroquine could reduce the expression of CD۳۱ and Ki۶۷ and increase the expression of caspase ۳. Conclusion: Apatinib inhibits proliferation and induces apoptosis in H۱۹۷۵ and H۱۴۴۶ lung cancer cells with high VEGFR۲ expression and autophagy in H۱۹۷۵ and H۴۴۶ cells.

Keywords:

Apatinib mesylate , Apoptosis , Autophagy , Lung Neoplasms , Cell Proliferation , VEGFR۲