Anlotinib inhibits the proliferation, migration and invasion, and induces apoptosis of breast cancer cells by downregulating TFAP2C.

Abstract

The vascular endothelial growth factor receptor (VEGFR) network contributes to breast cancer pathogenesis and progression. Anlotinib is a highly potent multi-target tyrosine kinase inhibitor that has been previously shown to exert antitumor effects in various types of cancer. The aim of the present study is to investigate the effect of Anlotinib against breast cancer cells in vitro and uncover the possible underlying mechanisms. The human breast cancer cell line MCF-7 was treated with different concentrations of Anlotinib, before cell proliferation, migration, invasion and apoptosis were assessed using colony formation, wound healing, Transwell and TUNEL staining assays. In addition, the expression of transcription factor AP-2γ (TFAP2C) following Anlotinib stimulation was measured using reverse transcription-quantitative PCR and western blot analysis. TFAP2C was overexpressed in MCF-7 using transfection with a pcDNA3.1 vector, before the aforementioned experiments were repeated. The results revealed that Anlotinib impaired cell viability and colony formation, reduced proliferating cell nuclear antigen, Ki-67, MMP2, MMP9 and Bcl-2 expression levels, and inhibited cell migration and invasion. By contrast, the expression levels of tissue inhibitor of metalloproteinase 1, the frequency of apoptotic cells, the expression of Bax and the cleaved caspase-3/caspase-3 ratio increased in a concentration-dependent manner. Additionally, the expression of TFAP2C decreased after Anlotinib treatment. However, TFAP2C overexpression partially blocked the effects of Anlotinib on the proliferation, migration, invasion and apoptosis of MCF-7 cells. To conclude, Anlotinib suppressed proliferation, migration and invasion, whilst inducing apoptosis of MCF-7 cells, which may be partially dependent on the inhibition of TFAP2C expression.