Marked improvement of cytotoxic effects induced by docetaxel on highly metastatic and androgen-independent prostate cancer cells by downregulating macrophage inhibitory cytokine-1.
Marked improvement of cytotoxic effects induced by docetaxel on highly metastatic and androgen-independent prostate cancer cells by downregulating macrophage inhibitory cytokine-1.
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多西他赛通过下调巨噬细胞抑制性细胞因子1，对多西他赛引起的细胞毒性作用明显改善。
DOI：
10.1038/bjc.2012.484
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发表时间：
2013-03-19
影响因子：
8.8
通讯作者：
Batra, S. K.
中科院分区：
文献类型：
--
作者：
Mimeault, M.;Johansson, S. L.;Batra, S. K.
关键词：
巨噬细胞抑制细胞因子-1 （MIC-1）的过度表达经常发生在前列腺癌（PC）向雄激素非依赖性（AI）和转移性疾病的进展过程中，并与患者的不良预后相关。对MIC-1的功能增益和功能丧失进行了分析，以确定其对转移性和AI PC细胞的侵袭性和化疗耐药表型的影响，以及其下调对逆转多西他赛耐药的益处。结果表明，PC3细胞中分泌的MIC-1蛋白水平的提高与它们获得上皮-间质转化特征、更高的侵袭能力和多西他赛耐药性有关。重要的是，MIC-1在LNCaP-LN3和PC3M-LN4细胞中的下调显著降低了其侵袭能力，促进了多西紫杉醇诱导的抗增殖、抗侵袭以及线粒体和caspase依赖性的凋亡作用。PC3M-LN4细胞中MIC-1的下调也能有效促进多西他赛对具有干细胞样特性的侧群（SP）和PC3M-LN4细胞的非SP细胞部分的细胞毒性作用。这些数据表明，MIC-1的下调可能是一种潜在的治疗策略，可以提高目前以多西他赛为基础的化疗的疗效，消除PC细胞的总质量，从而防止PC患者的疾病复发和死亡。
Overexpression of macrophage inhibitory cytokine-1 (MIC-1) frequently occurs during the progression of prostate cancer (PC) to androgen-independent (AI) and metastatic disease states and is associated with a poor outcome of patients. The gain- and loss-of-function analyses of MIC-1 were performed to establish its implications for aggressive and chemoresistant phenotypes of metastatic and AI PC cells and the benefit of its downregulation for reversing docetaxel resistance. The results have indicated that an enhanced level of secreted MIC-1 protein in PC3 cells is associated with their acquisition of epithelial–mesenchymal transition features and higher invasive capacity and docetaxel resistance. Importantly, the downregulation of MIC-1 in LNCaP-LN3 and PC3M-LN4 cells significantly decreased their invasive capacity and promoted the antiproliferative, anti-invasive and mitochrondrial- and caspase-dependent apoptotic effects induced by docetaxel. The downregulation of MIC-1 in PC3M-LN4 cells was also effective in promoting the cytotoxic effects induced by docetaxel on the side population (SP) endowed with stem cell-like properties and the non-SP cell fraction from PC3M-LN4 cells. These data suggest that the downregulation of MIC-1 may constitute a potential therapeutic strategy for improving the efficacy of current docetaxel-based chemotherapies, eradicating the total mass of PC cells and thereby preventing disease relapse and the death of PC patients.
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影响因子：
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作者：
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Roy-Burman, Pradip
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作者：
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通讯作者：
Tang, D. G.