Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2
Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2
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环孢素 A 通过下调丙酮酸激酶 M2 亚型的表达抑制乳腺癌细胞生长
DOI：
10.3892/ijmm.2012.989
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发表时间：
2012-08-01
影响因子：
5.4
通讯作者：
Wang, Qingqing
中科院分区：
文献类型：
--
作者：
Jiang, Kai;He, Baoming;Wang, Qingqing
肿瘤细胞的高增殖率导致了与正常细胞不同的代谢需求。一种胚胎和肿瘤特异性的丙酮酸激酶M2(PKM2)在癌细胞中过表达，以增加大分子生物合成和肿瘤生长中糖酵解中间体的使用。我们报道环孢菌素A(CsA)可以调节乳腺癌细胞株MCF-7、MDA-MB-435和MDA-MB-231中PKM2的表达和活性。与正常原代乳腺细胞相比，PKM2在三种乳腺癌细胞系中高表达。CsA以时间和剂量依赖的方式抑制乳腺癌细胞的活性。CsA显著下调乳腺癌细胞中PKM2的表达，减少三磷酸腺苷(ATP)的合成，从而导致癌细胞发生坏死。此外，CsA对乳腺癌MCF-7细胞的生长抑制作用减弱，提示CsA是一种有效的抑制PKM2依赖的乳腺癌细胞增殖的方法。这些结果可能为CsA在癌症治疗中的作用机制提供新的见解。
The high proliferative rate of tumor cells leads to metabolic needs distinct from those of their normal counterparts. An embryonic- and tumor-specific isoform of the enzyme pyruvate kinase M2 (PKM2) is overexpressed in cancer cells to increase the use of glycolytic intermediates for macromolecular biosynthesis and tumor growth. We report that Cyclosporin A (CsA) can regulate the expression and activity of PKM2 in breast cancer cell lines MCF-7, MDA-MB-435 and MDA-MB-231. PKM2 was found to be highly expressed in the three breast cancer cell lines compared to normal primary breast cells. Treatment with CsA inhibited the viability of breast cancer cells in a time- and dose-dependent manner. CsA significantly downregulated the expression of PKM2 in breast cancer cells and decreased adenosine triphosphate (ATP) synthesis, which induced cancer cells to undergo necrosis. Furthermore, the growth suppression effect of CsA was impaired in MCF-7 cells when they were transfected with the PKM2 overexpression plasmid, suggesting that CsA was an effective inhibitor of PKM2-dependent proliferation of breast cancer cells. These results may provide new insights into the mechanism of CsA in cancer therapy.