阿帕替尼通过抑制糖酵解途径对乳腺癌MDA-MB-231细胞增殖抑制及凋亡的作用

张化芝; 李晓双; 郭晓烨; 赵明池

doi:10.3971/j.issn.1000-8578.2019.18.1422

阿帕替尼通过抑制糖酵解途径对乳腺癌MDA-MB-231细胞增殖抑制及凋亡的作用

Apatinib Suppresses Proliferation and Induced Apoptosis of Human Breast Cancer Cell Line MDA-MB-231 Through Glycolytic Inhibition

摘要

摘要:
目的探讨阿帕替尼体外水平抗乳腺癌作用及其机制。
方法采用CCK-8法检测阿帕替尼对乳腺癌MDA-MB-231细胞的增殖抑制作用；采用Annexin V-FITC/PI凋亡检测试剂盒检测阿帕替尼对乳腺癌MDA-MB-231细胞凋亡的影响；采用乳酸含量检测试剂盒检测阿帕替尼对乳腺癌MDA-MB-231细胞内乳酸产量的影响；采用糖酵解压力试剂盒检测阿帕替尼对乳腺癌细胞MDA-MB-231细胞外酸化速率的影响。
结果阿帕替尼可浓度依赖性地抑制乳腺癌MDA-MB-231细胞体外增殖（P < 0.05），作用48 h的半数抑制浓度IC₅₀为1.56 μmol/L；阿帕替尼可浓度依赖性地诱导MDA-MB-231细胞凋亡（P < 0.05）；阿帕替尼可浓度依赖性地抑制MDA-MB-231细胞内乳酸产量（P < 0.05）；阿帕替尼干预可抑制MDA-MB-231细胞的糖酵解能力值及糖酵解保留值，降低MDA-MB-231细胞外酸化速率（P < 0.05）。
结论阿帕替尼可能通过抑制乳腺癌MDA-MB-231细胞的有氧糖酵解效应，进而诱导其凋亡。

Abstract:
Objective To investigate the antitumor effect of apatinib on breast cancer cells in vitro and its mechanism.
Methods CCK-8 assay was used to detect the inhibitory effect of apatinib on the proliferation of breast cancer cell line MDA-MB-231. Annexin V-FITC/PI apoptosis detection kit was used to detect the effect of apatinib on the apoptosis of MDA-MB-231 cells. The effect of apatinib on lactate production in MDA-MB-231 cells was detected by lactate content assay kit. The effect of apatinib on the extracellular acidification rate of MDA-MB-231 cells was detected by glycolysis stress test kit.
Results Apatinib inhibited the proliferation of breast cancer MDA-MB-231 cells in vitro in a concentration-dependent manner (P < 0.05). The half maximal inhibitory concentration (IC₅₀) of apatinib in MDA-MB-231 cells was 1.56μmol/L for 48h treatment. Apatinib also induced the apoptosis of MDA-MB-231 cells in a concentration-dependent manner (P < 0.05). Apatinib inhibited intracellular lactate content in MDA-MB-231 cells in a concentration-dependent manner (P < 0.05). Apatinib also decreased extracellular acidification rate of MDA-MB-231 cells, including glycolytic capacity and glycolytic reserve (P < 0.05).
Conclusion Apatinib could induce the apoptosis of breast cancer cell line MDA-MB-231 by inhibiting aerobic glycolysis.

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