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

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1.56μmol/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。

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

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.