br Previous studies indicated that
Previous studies indicated that apatinib could inhibit metastasis and tumorigenesis in patients with TNBC [3,22,23]. In this study, apatinib enhanced the pro-apoptotic, anti-migratory and anti-invasive eﬀects of cisplatin on MDA-MB-231 cells. In addition, apatinib is an anti-angio-genic drug and a small-molecule inhibitor of VEGFR2, which could markedly inhibit VEGF signaling pathway [24,25]. Moreover, apatinib induced cell apoptosis and inhibited cell proliferation via blocking VEGF pathway [26,27]. Prior study also demonstrated that apatinib induce apoptosis in intrahepatic cholangiocarcinoma via inhibiting VEGF signaling . Thus, we hypothesized that apatinib enhance the pro-apoptotic, anti-migratory and anti-invasive eﬀects of cisplatin in TNBC through VEGFR2 signaling. Our results indicated that cisplatin has no eﬀect on the 2-NBDG of p-VEGFR2, while combination cis-platin with apatinib significantly decreased the expressions of p-VEGFR2. Therefore, we supposed that apatinib could enhance the anti-tumor eﬀect of cisplatin via VEGFR2. Whether other factors are in-volved in this process needs to be clarified.
Angiogenesis and PI3K/Akt/mTOR pathway are the major mole-cular targets for the treatment of breast cancer . Hong et al illu-strated that VEGF activated VEGFR2 and initiated a PI3K-AKT-mTOR pathway, which exhibited an anti-apoptotic eﬀect . Inhibition of angiogenesis through the blocking of the VEGFR2-Akt-mTOR signaling pathway has exerted as a potential method in anti-tumor therapy [29,30]. In this study, we also found that cisplatin decreased the ex-pressions of p-Akt and p-mTOR, while the levels of these proteins were further reduced in the presence of apatinib. Therefore, the possible mechanism was that apatinib decreased the VEGF-mediated Akt/mTOR signaling activity. Thus, we infer that intracellular VEGFR2 inhibitors, apatinib, could enhance the anti-tumor eﬀect of cisplatin via VEGFR2-Akt-mTOR signaling pathway.
In conclusion, apatinib enhanced the anti-tumor eﬀects of cisplatin on MDA-MB-231 cells via inhibition of VEGFR2. The results suggested that the combination of apatinib with cisplatin may serve as a potential method in the treatment of patients with TNBC.
Conflict of interest
The present study was supported by a grant from Clinical research of general medicine of China (grant no. 2016QK013). The authors thank Dr liuhao (Bengbu Medical College) for his helpful discussions.
 M. Huang, B. Huang, G. Li, S. Zeng, Apatinib aﬀect VEGF-mediated cell prolifera-tion, migration, invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT
 M. Ducreux, P. Osterlund, J.P. Pignon, Angiogenesis inhibition in the second-line treatment of metastatic colorectal cancer-A definite conclusion? Semin. Oncol. 44
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Apatinib exerts anti-tumour effects on ovarian cancer cells
a Department of Gynecology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150040, Heilongjiang Province, China
b Beijing Center for Physical and Chemical Analysis, No. 7 Fengxianzhong Road, Haidian District, Beijing 100094, China
• Apatinib does not appreciably affect the proliferation and vitality of ovarian cancer cells.
• Apatinib inhibits ovarian cancer cells migration.
• Apatinib suppresses the epithelial-mesenchymal transition (EMT).
• Apatinib inhibits the JAK/STAT3, PI3K/Akt and Notch signalling pathways.
• Apatinib inhibits tumour growth in vivo.