The expression of URGCP gene in prostate cancer cell lines: correlation with rapamycin

The expression of URGCP gene in prostate cancer cell lines: correlation with rapamycin
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DOI:
10.1007/s11033-012-1891-6
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发表时间:
2012-12-01
影响因子:
2.8
通讯作者:
Gunduz, Cumhur
Gunduz, Cumhur
中科院分区:
生物学4区
文献类型:
--
作者:
Dodurga, Yavuz;Avci, Cigir Biray;Gunduz, Cumhur

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前列腺癌的分子靶点正在不断探索,目前几乎没有治疗选择。雷帕霉素(Rapamycin,RPM)是从吸水链霉菌(Streptomyceshygroscopicus)中分离得到的一种大环内酯类抗生素,能抑制G1期向S期的转化。URGCP(upregulator of cell proliferation)是位于染色体7 p13上的一个新基因。我们的目的是研究URGCP基因表达变化在有/无RPM的PC 3、DU 145和LNCAP细胞系中的作用。采用台盼蓝拒染法和XTT法检测雷帕霉素对细胞的平均存活率和细胞毒作用。雷帕霉素对DU 145、PC 3和LNCAP细胞的细胞毒性作用呈时间和剂量依赖性,IC 50在1-100 nM范围内。评估结果时,检测到DU 145、PC 3和LNCaP细胞中的IC 50剂量分别为10、25和50 nM。DU 145、LNCAP和PC 3细胞中URGCP基因表达的平均相对比值分别为-1.48、6.59和-13.00。DU 145、LNCAP和PC 3中的错误发现率调整p值分别为1.25 x 10(-5)、2.20 x 10(-8)和6.20 x 10(-9)。当比较剂量组和对照组之间的URGCP基因表达水平时,我们发现DU 145和PC 3细胞的剂量组中URGCP基因表达显著降低。
Molecular targets in prostate cancer are continually being explored, for which there are currently few therapeutic options. Rapamycin (RPM) is an antifungal macrolide antibiotic isolated from Streptomyces hygroscopicus which can inhibit the G1 to S transition. URGCP (upregulator of cell proliferation) is a novel gene located on chromosome 7p13. We aimed to investigate the role of URGCP gene expression changes in PC3, DU145, and LNCAP cell lines with/out RPM. Average cell viability and cytotoxic effect of rapamycin were investigated at 24 h intervals for three days by using Trypan blue dye exclusion test and XTT assay. Cytotoxic effects of rapamycin in DU145, PC3 and LNCAP cells were detected in time and dose dependent manner with the IC50 doses within the range of 1-100 nM. As the results were evaluated, IC50 doses in the DU145, PC3, and LNCaP cells were detected as 10, 25, and 50 nM, respectively. The mean relative ratios of URGCP gene expression in DU145, LNCAP and PC3 cells were found as -1.48, 6.59 and -13.00, respectively, when compared to rapamycin-free cells. The False Discovery Rate adjusted p value in DU145, LNCAP and PC3 were 1.25 x 10(-5), 2.20 x 10(-8) and 6.20 x 10(-9), respectively. When the URGCP gene expression level is compared between the dose and control group, we found that URGCP gene expression was significantly decreased in dose groups of DU145 and PC3 cells.