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阿帕替尼对卵巢癌细胞发挥抗肿瘤作用。

Apatinib exerts anti-tumour effects on ovarian cancer cells.

机构信息

Department of Gynecology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150040, Heilongjiang Province, China.

Beijing Center for Physical and Chemical Analysis, No. 7 Fengxianzhong Road, Haidian District, Beijing 100094, China.

出版信息

Gynecol Oncol. 2019 Apr;153(1):165-174. doi: 10.1016/j.ygyno.2019.01.010. Epub 2019 Jan 14.

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.

摘要

目的

血管内皮生长因子受体-2(VEGFR-2)酪氨酸激酶小分子抑制剂阿帕替尼对多种肿瘤具有强烈的抗肿瘤活性。然而,阿帕替尼在卵巢癌中的作用尚不清楚。本研究旨在探讨阿帕替尼在体外和体内调节卵巢癌细胞生物学功能的作用及其潜在机制。

方法

通过评估细胞活力、迁移和侵袭来确定阿帕替尼对卵巢癌细胞的影响。使用流式细胞术分析卵巢癌细胞的细胞周期分布和凋亡。采用 Western blot 检测信号通路标志物的水平。利用小鼠异种移植模型评估阿帕替尼抑制肿瘤生长的疗效。

结果

阿帕替尼对卵巢癌细胞的增殖和活力没有明显影响,但能抑制卵巢癌细胞的迁移。阿帕替尼通过抑制 JAK/STAT3、PI3K/AKT 和 Notch 信号通路抑制卵巢癌细胞的上皮间质转化。阿帕替尼在体内有效抑制肿瘤生长。

结论

根据我们的研究结果,阿帕替尼是一种高效、口服活性的抗血管生成和抗卵巢癌药物。

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