The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential.
The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential.
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维生素D模拟MART-10减弱了三层阴性乳腺癌细胞的转移性潜力。
DOI：
10.3390/ijms17040606
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发表时间：
2016-04-21
影响因子：
5.6
通讯作者：
Juang HH
中科院分区：
文献类型：
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作者：
Chiang KC;Yeh TS;Chen SC;Pang JH;Yeh CN;Hsu JT;Chen LW;Kuo SF;Takano M;Kittaka A;Chen TC;Sun CC;Juang HH
关于乳腺癌治疗，三阴性乳腺癌（TNBC）是一个难题。大多数TNBC患者死于癌症转移。因此，迫切需要开发一种新的方案来减弱TNBC转移潜力。MART-10（19-nor-2α-（3-hydroxypropyl）-1，25（OH）2D 3）是新合成的1α，25（OH）2D 3类似物，具有比1α，25（OH）2D 3更强的肿瘤生长抑制作用，且在体内具有活性，无明显毒副作用。本研究证明1α，25（OH）2D 3和MART-10均能有效抑制TNBC细胞的迁移和侵袭，其中MART-10更有效。MART-10和1α，25（OH）2D 3诱导MDA-MB-231细胞中钙粘蛋白转换（上调E-钙粘蛋白和下调N-钙粘蛋白）和下调P-钙粘蛋白表达。MART-10通过抑制Zeb 1、Zeb 2、Slug和Twist表达来抑制MDA-MB-231细胞中的EMT（上皮间质转化）过程。在乳腺癌细胞中，首次发现1α，25（OH）2D 3和MART-10对乳腺癌转移刺激因子LCN 2有抑制作用。基质金属蛋白酶-9（MMP-9）活性也被MART-10下调。此外，MDA-MB-231细胞中的F-肌动蛋白合成随着1α，25（OH）2D 3和MART-10的暴露而减弱。基于我们的结果，我们得出结论，MART-10可以有效地抑制TNBC细胞的转移潜力，值得进一步研究作为一种新的方案来治疗TNBC。
Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3), the newly-synthesized 1α,25(OH)2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)2D3 induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin) and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition) process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH)2D3 and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9) activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH)2D3 and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC.