Treatment of prostate cancer cells with adenoviral vector-mediated antisense RNA using androgen-dependent and androgen-independent promoters

Treatment of prostate cancer cells with adenoviral vector-mediated antisense RNA using androgen-dependent and androgen-independent promoters
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使用雄激素依赖性和雄激素非依赖性启动子用腺病毒载体介导的反义RNA治疗前列腺癌细胞

DOI:
10.1007/s12032-009-9243-7
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发表时间:
2010-06
期刊:
影响因子:
3.4
通讯作者:
Li, Wei
Li, Wei
中科院分区:
医学4区
文献类型:
--
作者:
Li, Wei

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本研究旨在开发一种新的反义前列腺癌治疗方法。我们构建了前列腺特异性雄激素依赖性启动子(pADxsi-P2-pADxMetDC-ODC-PolyA)和前列腺特异性雄激素非依赖性启动子(pADxsi-P1-pADxMetDC-ODC-PolyA)介导的ODC/pADxMetDC双反义RNA重组腺病毒。Western blot分析检测ODC和METDC蛋白水平。MTT法测定各组细胞的生长曲线。流式细胞仪检测细胞凋亡、增殖和细胞周期分布,以证明重组腺病毒对前列腺癌细胞的影响。RT-PCR、Western blotting、MTT和裸鼠肿瘤生长抑制实验表明,pADxsi-P1-pADxMetDC-ODC-PolyA和pADxsi-P2-pADxMetDC-ODC-PolyA在基因和蛋白水平均能抑制细胞增殖。同时,pADxsi-P2-pADxMetDC-ODC-PolyA的抑制作用比pADxsi-P1-pADxMetDC-ODC-PolyA载体的抑制作用更显著。两种腺病毒载体对前列腺肿瘤的生长均表现出显著的抑制作用,并且pADxsi-P2-pADxMetDC-ODC-PolyA载体的抑制作用强于pADxsi-P1-pADxMetDC-ODC-PolyA载体。
The present study was designed to develop a novel antisense approach to prostate cancer therapy. We constructed ODC/AdoMetDC double antisense RNA recombinant adenovirus mediated by a prostate-specific androgen-dependent promoter (pADxsi-P2-AdoMetDC-ODC-PolyA) or a prostate-specific androgen-independent promoter (pADxsi-P1-AdoMetDC-ODC-PolyA). Western blot analysis was performed to detect the ODC and AdoMetDC protein levels. The growth curves for each group of cells were determined by MTT assay. Flow cytometry was conducted to detect cell apoptosis, proliferation, and cell cycle distribution in order to demonstrate the effects of the recombinant adenoviruses on the prostate cancer cells. RT-PCR, Western blotting, MTT, and tumor growth inhibition assay in nude mice demonstrated that pADxsi-P1-AdoMetDC-ODC-PolyA and pADxsi-P2-AdoMetDC-ODC-PolyA exhibited inhibitory effects on cell proliferation at both the gene and protein levels. Meanwhile, inhibiting effects of the pADxsi-P2-AdoMetDC-ODC-PolyA is more profound than those of the pADxsi-P1-AdoMetDC-ODC-PolyA vector. Both of the adenoviral vectors exhibited significant inhibitory effects on the growth of prostate tumors, and the inhibitory effects of the pADxsi-P2-AdoMetDC-ODC-PolyA vector were stronger than those of the pADxsi-P1-AdoMetDC-ODC-PolyA vector.
DOI: 10.1016/0304-3835(95)03860-y
发表时间: 1995-08
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影响因子: 9.7
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发表时间: 2022-08
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发表时间: 1992-01-01
期刊: PROSTATE
影响因子: 2.8
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