阿帕替尼通过促进Fas向脂筏内聚集诱导乳腺癌细胞凋亡

doi:10.5246/jcps.2019.11.074

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (11): 778-785.DOI: 10.5246/jcps.2019.11.074

阿帕替尼通过促进Fas向脂筏内聚集诱导乳腺癌细胞凋亡

闫顺朝^1*, 焦昕², 李娜¹, 杜扬帆¹, 姜程遥¹

1. 中国医科大学附属盛京医院肿瘤科, 辽宁沈阳 110022
2. 沈阳市胸科医院呼吸科, 辽宁沈阳 110044

收稿日期:2019-07-28 修回日期:2019-08-19 出版日期:2019-12-01 发布日期:2019-09-15
通讯作者: Tel.: +86-24-96615-63115, E-mail: yan50@illinois.edu
基金资助:
The Science and Technology Foundation of Shenyang City (Grant No. RC170545), the Science and Technology Foundation of Liaoning Province (Grant No. 20170540995), and the National Science Foundation of China (Grant No. 81302313).

Apatinib induces apoptosis of breast cancer cells by redistribution of Fas into lipid rafts

Shunchao Yan^1*, Xin Jiao², Na Li¹, Yangfan Du¹, Chengyao Jiang¹

1. Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, China
2. Department of Respiratory Medicine, Shenyang Chest Hospital, Shenyang 110044, China

Received:2019-07-28 Revised:2019-08-19 Online:2019-12-01 Published:2019-09-15
Contact: Tel.: +86-24-96615-63115, E-mail: yan50@illinois.edu
Supported by:
The Science and Technology Foundation of Shenyang City (Grant No. RC170545), the Science and Technology Foundation of Liaoning Province (Grant No. 20170540995), and the National Science Foundation of China (Grant No. 81302313).

摘要/Abstract

摘要：

阿帕替尼是一种口服的抗肿瘤药物, 其在很多肿瘤中均有活性, 但其抗肿瘤的作用机制复杂, 至今不清, 本研究拟评估其在乳腺癌中的作用, 并探索可能的机制。本研究利用CCK-8方法检测细胞的活力, 流式细胞术检测细胞的凋亡, Western Blot方法检测PARP, caspase-8的表达, 免疫荧光检测脂筏的聚集情况。研究结果显示, 阿帕替尼可以剂量依赖的方式抑制乳腺癌细胞增殖。进一步研究发现阿帕替尼可促进脂筏的聚集和Fas向脂筏内分重新分布, 脂筏抑制剂预处理后抑制了Fas向脂筏内的分布和阿帕替尼诱导的凋亡。总之, 我们的研究结果首次证实阿帕替尼可通过促进死亡受体Fas向脂筏内的聚集诱导乳腺癌细胞凋亡。

关键词: 阿帕替尼, 乳腺癌, 脂筏, Fas

Abstract:

Apatinib, an oral anti-angiogenic agent, has been shown to have anti-cancer effects for several cancer cell types. However, little is known about the direct anti-tumor activity of apatinib for breast cancer cells. Herein, the direct effect of apatinib on breast cancer cells and its mechanism of action were assessed. Cell viability was measured with a Cell Counting Kit-8. Cell apoptosis was assessed by flow cytometry. The expression of caspase-8 and the cleavage of poly ADP ribose polymerase were assessed by Western blotting analysis. Lipid rafts and Fas distribution were determined by immunofluorescence microscopy. Apatinib suppressed breast cancer cell proliferation in a dose-dependent manner. Furthermore, apatinib enhanced the aggregation of lipid rafts and the redistribution of Fas into lipid rafts. Pretreatment with methyl-β-cyclodextrin, a cholesterol-sequestering agent, significantlyreversed Fas redistribution and apatinib-induced apoptosis.In conclusion, these results demonstrated that apatinib induced apoptosis of breast cancer cells partially through recruitment of Fas into lipid rafts.

Key words: Apatinib, Breast cancer, Lipid rafts, Fas

中图分类号:

R969

Supporting:

闫顺朝, 焦昕, 李娜, 杜扬帆, 姜程遥. 阿帕替尼通过促进Fas向脂筏内聚集诱导乳腺癌细胞凋亡[J]. 中国药学(英文版), 2019, 28(11): 778-785.

Shunchao Yan, Xin Jiao, Na Li, Yangfan Du, Chengyao Jiang. Apatinib induces apoptosis of breast cancer cells by redistribution of Fas into lipid rafts[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(11): 778-785.

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阿帕替尼通过促进Fas向脂筏内聚集诱导乳腺癌细胞凋亡

Apatinib induces apoptosis of breast cancer cells by redistribution of Fas into lipid rafts

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