Conclusion br In conclusion apatinib enhanced
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.
Objective. Apatinib, a small molecule inhibitor of VEGFR-2 tyrosine kinase, shows strong anti-tumour activity against various tumours. The function of apatinib in ovarian cancer, however, remains unclear. This study was conducted to investigate the effects and potential mechanisms by which apatinib modulates the biological func-tion of ovarian cancer cells in vitro and in vivo.
Methods. The effects of apatinib on ovarian cancer cells were determined by assessing cell viability, migration and invasion. The L-NAME hydrochloride distribution and apoptosis of ovarian cancer cells were analysed using flow cytome-try. Western blotting was performed to determine the levels of signalling pathway markers. A mouse xenograft model was used to evaluate the efficacy of apatinib in preventing tumour growth.
Results. Apatinib did not appreciably affect ovarian cancer cell proliferation and vitality, but did inhibit ovarian cancer cell migration. Apatinib suppressed the epithelial-mesenchymal transition in ovarian cancer cells by inhibiting the JAK/STAT3, PI3K/AKT and Notch signalling pathways. Apatinib effectively inhibited tumour growth in vivo.
Conclusion. Based on our findings, apatinib is a highly potent, orally active anti-angiogenic and anti-ovarian cancer agent.
Epithelial ovarian cancer (EOC) is the second most common gynaecologic cancer. It is the most fatal disease and the fifth leading cause of cancer-related death among women . Patients with ad-vanced EOC have a 5-year survival rate of only 40% . The standard treatment for EOC is surgical cytoreduction followed by adjuvant com-bination chemotherapy. Despite improvements in surgical and chemo-therapeutic approaches, the majority of women with relapsed EOC eventually die from the disease, and an unmet and urgent need to im-prove treatment exists.
Corresponding authors at: No. 150 Haping Road, Nangang District, Harbin 150040, Heilongjiang Province, China.
Anti-angiogenic therapy is one of the most promising methods for treating cancer. Apatinib, also known as YN968D1, is a new anti-angiogenic therapy agent that has been confirmed to be a safe and effec-tive small-molecule, anti-angiogenic, targeted drug for advanced gastric cancer [3,4]. Independent intellectual property rights for this compound were established in China in 2014. Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that selectively binds to and potently suppresses VEGFR-2 activity and then blocks VEGFR-2-mediated angiogenesis . As one of the most recently developed oral anti-angiogenic agents, apatinib shows encouraging preclinical and clinical results for the treat-ment of various solid tumours [5–10].
However, the mechanism underlying the effects of apatinib on ovar-ian cancer remains unclear. This study was designed to evaluate the ef-fects of apatinib on ovarian cancer cells both in vivo and in vitro and to investigate the characteristics and possible mechanisms of these effects.
Fig. 1. A The effect of apatinib on cell proliferation was determined by the MTT assay. B Flow cytometry assays were conducted to evaluate the effect of apatinib on cell cycle progression. C Flow cytometry assays were conducted to evaluate the effect of apatinib on apoptosis.