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 [27]. 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 [28]. Hong et al illu-strated that VEGF activated VEGFR2 and initiated a PI3K-AKT-mTOR pathway, which exhibited an anti-apoptotic effect [27]. 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.
5. Conclusion
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
Acknowledgements
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.
References
[26] 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
[30] 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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Gynecologic Oncology
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.
Article history:
Keywords:
Apatinib
Ovarian cancer