Apatinib enhanced anti-tumor activity of cisplatin on triple-negative breast cancer through inhibition of VEGFR-2

Background: Triple-negative breast cancer (TNBC) was known as a fast-growing and an aggressive tumor. Cisplatin is the effective cytotoxic drug used for the treatment of TNBC. In addition, apatinib, a VEGFR2 inhibitor, exhibits antitumor activity in patients with TNBC. However, the effects of combination of apatinib with cisplatin on TNBC remain unclear. Thus, this study aimed to investigate the effects of apatinib in combination with cisplatin on MDA-MB-231 cells. Methods: Immunohistochemistry was used to detect the expression of VEGFR2. In addition, CCK-8, flow cytometric, transwell assays were used to measure the cell proliferation, apoptosis, migration and invasion, respectively. Moreover, western blotting was used to detect the expressions of Bax, active caspase 3, p-VEGFR2, p-Akt and p-mTOR. Results: VEGFR2 was significantly upreguated in patients with TNBC. In addition, the inhibitory effects of cisplatin on the proliferation, migration and invasion of MDA-MB-231 cells were enhanced by apatinib. Moreover, apatinib increased cisplatin-induced apoptosis on MDA-MB-231 cells via increasing the level of Bax and active caspase 3 and decreasing the expression of Bcl-2. Importantly, apatinib enhanced anti-tumor effect of cisplatin on MDA-MB-231 cells via inhibiting the levels of p-VEGFR2, p-Akt and p-mTOR. Conclusion: Our findings indicated that apatinib enhanced the anti-tumor effects of cisplatin on MDA-MB-231 cells via inhibition of VEGFR2. Thus, the combination of apatinib with cisplatin may serve as a potential approach in the treatment of patients with TNBC.