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Journal of Chinese Pharmaceutical Sciences ›› 2019, Vol. 28 ›› Issue (11): 778-785.DOI: 10.5246/jcps.2019.11.074

• Original articles • Previous Articles     Next Articles

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

Shunchao Yan1*, Xin Jiao2, Na Li1, Yangfan Du1, Chengyao Jiang1   

  1. 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).

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

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