Chowdhury Kaushik, Sharma Ankit, Sharma Tanu, Kumar Suresh, Mandal Chandi C
a Department of Biochemistry, School of Life Sciences , Central University of Rajasthan , Ajmer , India.
Cancer Invest. 2017 Jul 3;35(6):403-413. doi: 10.1080/07357907.2017.1309548. Epub 2017 May 2.
Previous reports have documented that cholesterol-lowering simvastatin prevented osteolytic metastasis of breast cancer in animal model in which cancer cells were placed into blood circulation. Thus, simvastatin treatment might have a preventive effect in inhibiting osteoclast activity of metastatic bone microenvironment. This study documented that both simvastatin and MBCD (cholesterol depleting drug) blocked the breast cancer-induced TRAP and MMP activity, and expressions of various osteoclastogenic genes (TRAP, Cathepsin K, and NFATc1) in pre-osteoclast RAW264.7 cells, and osteoclastogenic CSF-1 and RANKL expressions in breast cancer MCF-7 cells. Thus, these findings unravel a molecular mechanism of simvastatin-/MBCD-mediated inhibition of breast cancer-driven osteoclast activity.
先前的报告已证明，在将癌细胞注入血液循环的动物模型中，降胆固醇药物辛伐他汀可预防乳腺癌的溶骨性转移。因此，辛伐他汀治疗可能对抑制转移性骨微环境中的破骨细胞活性具有预防作用。本研究证明，辛伐他汀和MBCD（胆固醇耗竭药物）均可阻断乳腺癌诱导的破骨细胞相关酸性磷酸酶（TRAP）和基质金属蛋白酶（MMP）活性，以及前破骨细胞RAW264.7细胞中各种破骨细胞生成基因（TRAP、组织蛋白酶K和活化T细胞核因子c1）的表达，以及乳腺癌MCF-7细胞中破骨细胞生成的集落刺激因子-1（CSF-1）和核因子κB受体活化因子配体（RANKL）的表达。因此，这些发现揭示了辛伐他汀/MBCD介导的抑制乳腺癌驱动的破骨细胞活性的分子机制。
