南方医科大学学报

南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (03): 355-.

• • 上一篇    下一篇

Hsp90抑制剂槚如酸对乳腺癌MDA-MB-231细胞增殖、侵袭、迁移的影响

李红梅，聂丽娟，霍强，赵素容，马涛，吴成柱，刘浩   

  • 出版日期:2015-03-20 发布日期:2015-03-20

Effect of anacardic acid, a Hsp90 inhibitor, on proliferation, invasion and migration of
breast cancer MDA-MB-231 cells

  • Online:2015-03-20 Published:2015-03-20

HTML

PDF

2467

摘要： 目的探讨热休克蛋白90 (Hsp90) 抑制剂槚如酸对人乳腺癌MDA-MB-231细胞增殖、侵袭、迁移的影响。方法采用体外
malachite green-molybdate 显色反应和ATP-琼脂糖凝胶结合实验检测槚如酸对Hsp90 抑制活性；MTT 法检测药物对
MDA-MB-231增殖抑制效应；Transwell小室法检测药物对细胞侵袭和迁移影响；免疫印迹法检测药物对相关蛋白基质金属蛋
白酶-9（MMP-9）、基质金属蛋白酶组织抑制剂-1（TIMP-1）、Hsp90、热休克蛋白70（Hsp70）表达的影响。结果槚如酸为特异性
的Hsp90抑制剂，其抑制IC50值为82.5 μmol/L。MTT结果显示，槚如酸具有明显抑制细胞增殖的作用，且呈现浓度依赖关系，其
IC50值为29.3 μmol/L。不同浓度的槚如酸（12.5，25.0，50.0 μmol/L）处理36 h后，与对照组相比，药物对细胞侵袭抑制率分别为：
23.6%、56.6%、67.0%，P<0.05。槚如酸（12.5，25.0，50.0 μmol/L）处理24 h 后，与对照组相比，药物对细胞迁移抑制率分别为：
30.0%、45.5%、77.5%，P<0.05。免疫印迹法结果显示，槚如酸随着浓度的增加，诱导MMP-9降解越明显，而对Hsp90和Hsp70蛋
白表达均没有影响。结论槚如酸能明显抑制乳腺癌细胞增殖、侵袭、迁移能力，其机制可能是通过抑制Hsp90 ATPase活性以
及导致下游的顾客蛋白的MMP-9表达下调有关。

Abstract: Objective To explore the effect of the Hsp90 inhibitor anacardic acid on cell proliferation, invasion and migration of
breast cancer MDA-MB-231 cells. Methods The inhibitory effect of anacardic acid on Hsp90 was assessed with in vitro ATPase
inhibition assay and ATP-sepharose binding assay. MTT assay was used to detect the growth inhibition induced by anacardic
acid in MDA-MB-231 cells. Transwell assays were used to evaluate MDA-MB-231 cell invasion and migration. Western blotting
was performed to assess the effect of anacardic acid in triggering the degradation of MMP-9, TIMP-1, Hsp90, and Hsp70.
Results Anacardic acid exhibited a modest activity of ATPase inhibition with an IC50 value of 82.5 μmol/L. Anacardic acid
significantly suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner (IC50 value of 29.3 μmol/L).
Treatment with 12.5, 25, and 50 μmol/L anacardic acid for 36 h caused inhibition of cell invasion by 23.6%, 56.6%, and 67.0% in
MDA-MB-231 cells, respectively (P<0.05), and anacardic acid treatment for 24 h inhibited the cell migration by 30.0%, 45.5%,
and 77.5%, respectively (P<0.05). Anacardic acid dose-dependently induced MMP-9 degradation, but did not obviously affect
Hsp90 or Hsp70 expressions. Conclusion Anacardic acid can significantly inhibit the proliferation, invasion, and migration of
MDA-MB-231 cells, the mechanism of which may involve the inhibition of Hsp90 ATPse activity and down-regulation of
MMP-9 expression.