Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells
Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells
复制标题
microRNA-21参与介导雄激素非依赖性前列腺癌PC3细胞对多西紫杉醇的化疗耐药
DOI：
10.1038/aps.2010.48
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发表时间：
2010-07-01
影响因子：
8.2
通讯作者：
Ma, Chun-guang
中科院分区：
文献类型：
--
作者：
Shi, Guo-hai;Ye, Ding-wei;Ma, Chun-guang
目的：探讨microRNA-21是否参与了前列腺癌细胞对多西紫杉醇的化疗耐药。方法：采用微阵列技术检测多西他赛耐药PC3细胞的miRNA谱。采用Real-time PCR对阵列结果进行验证。合成miR-21模拟物和抑制剂，并使用Lipofectamine 2000引入细胞。CCK-8法检测细胞增殖。构建了含有pdcd3 ' UTR的荧光素酶报告基因，并用双荧光素酶法检测其活性。Western blot检测PDCD4蛋白表达。结果：建立了耐多西他赛前列腺癌PC3细胞株（PC3R）。使用微阵列，miR-21在PC3R细胞中被上调。miR-21的异位表达增加了PC3野生型细胞对多西紫杉醇的耐药性。相反，PC3R细胞中miR-21的沉默使细胞对多西紫杉醇敏感。mir -21沉默细胞和对照细胞的IC 50值分别为28.31和35.89 nmol/L。PDCD4是miR-21的直接靶基因，可介导PC3细胞对多西紫杉醇的化疗耐药。结论：我们的研究结果表明，miR-21促进了PC3细胞对多西紫杉醇的耐药，靶向miR-21可能为前列腺癌对多西紫杉醇治疗增敏提供了一种有希望的治疗方法。
Aim:To investigate whether microRNA-21 was involved in mediating the chemoresistance of prostate cancer cells to docetaxel.Methods:A microarray technique was used to determine the miRNA profile in docetaxel-resistant PC3 cells. Real-time PCR was used to confirm the array results. miR-21 mimics and inhibitors were synthesized and introduced to cells using Lipofectamine 2000. Cell proliferation was examined with the CCK-8 assay. Luciferase reporter containing PDCD 3′ UTR was constructed and the activity was detected by a dual luciferase assay. PDCD4 protein expression was evaluated using Western blot.Results:A docetaxel-resistant prostate cancer PC3 cell line (PC3R) was established. Using microarrays, miR-21 was found to be up-regulated in PC3R cells. Ectopic expression of miR-21 increased the resistance to docetaxel in PC3 wild type cells. In contrast, silencing of miR-21 in PC3R cells sensitized the cells to docetaxel. The IC 50 values for miR-21-silencing cells and control cells were 28.31 and 35.89 nmol/L, respectively. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells.Conclusion:Our findings suggest that miR-21 contributed to the resistance of PC3 cells to docetaxel, and that targeting miR-21 may offer a promising therapeutic approach in sensitizing prostate cancer to docetaxel treatment.