Jing Ding1, Xiao-Yan Cheng2, Shuang Liu1, Hong-Ying Ji1, Mu Lin1, Rong Ma3, Fan-Ling Meng4. 1. Department of Gynecology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150040, Heilongjiang Province, China. 2. Beijing Center for Physical and Chemical Analysis, No. 7 Fengxianzhong Road, Haidian District, Beijing 100094, China. 3. Department of Gynecology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150040, Heilongjiang Province, China. Electronic address: dr_marong2017@126.com. 4. Department of Gynecology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150040, Heilongjiang Province, China. Electronic address: dr_mfl1979@126.com.
Abstract
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 function 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 cell cycle distribution and apoptosis of ovarian cancer cells were analysed using flow cytometry. 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.
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 function 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 cell cycle distribution and apoptosis of ovarian cancer cells were analysed using flow cytometry. 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.