Silencing Poly (ADP-Ribose) Glycohydrolase (PARG) Expression Inhibits Growth of Human Colon Cancer Cells In Vitro via PI3K/Akt/NFκ-B Pathway

Silencing Poly (ADP-Ribose) Glycohydrolase (PARG) Expression Inhibits Growth of Human Colon Cancer Cells In Vitro via PI3K/Akt/NFκ-B Pathway
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沉默聚 (ADP-核糖) 糖水解酶 (PARG) 表达通过 PI3K/Akt/NFκ-B 通路抑制体外人结肠癌细胞的生长

DOI:
10.1007/s12253-011-9428-1
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发表时间:
2012
影响因子:
2.8
通讯作者:
Juan Pan
Juan Pan
中科院分区:
医学4区
文献类型:
--
作者:
N. J. Fauzee;Qiaozhuan Li;Yalan Wang;Juan Pan

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与聚adp -核糖糖水解酶(PARG)密切相关的聚adp -核糖聚合酶(PARP)在实验和临床癌症试验中都得到了深入的研究。然而,在本实验中,强调了PARG表达的重要性;通过慢病毒载体介导的短发夹RNA (shRNA)使其沉默。MTT实验显示,转染后的Lovo细胞G0/G1期细胞数量增加,S期细胞数量减少,对人Lovo结肠癌细胞生长有抑制作用。此外,我们的研究结果表明,沉默PARG的作用导致PARP表达受到抑制;与核因子κ b (nf - κ b)表达减少和Akt473磷酸化增加有关;提示磷酸肌醇3-激酶(PI3K)/Akt/NFκ-B通路在细胞生长和增殖中起重要作用。因此,本研究强调并集中于沉默PARG通过PI3K/Akt/NFκ-B途径抑制人结肠癌细胞生长的相关性;由于结肠癌仍然是世界上最常见的癌症之一,发病率和死亡率都很高。
Poly ADP-ribose polymerase (PARP) which is closely related to Poly ADP-ribose glycohydrolase (PARG) has already been thoroughly investigated in both experimental and clinical cancer trials compared to the latter. Nevertheless, in this experiment the importance of PARG expression was highlighted; whereby it is being silenced via lentivirus vector-mediated short hairpin RNA (shRNA). MTT assay showed that there was an inhibition in human Lovo colon cancer cell growth and flow cytometry demonstrated an increase in the population of cells in G0/G1 phase with a decrease in the S phase in transfected Lovo cells. Furthermore, our results suggested that the effect of silencing PARG leads to the inhibition of PARP expression; related to a decrease in the expression of Nuclear Factor Kappa-B (NFκ-B) with an increase in Akt473 phosphorylation; suggesting that the Phosphoinositol 3-kinase (PI3K)/Akt/NFκ-B pathway is important for cellular growth and proliferation. Hence, this study emphasizes and converges on the relevance of silencing PARG which inhibits growth of human colonic cancer cells via PI3K/Akt/NFκ-B pathway; as colon carcinoma remains to be amongst one of the commonest cancers throughout the world with high morbidity and mortality rates.
DOI: 10.1073/pnas.0406182101
发表时间: 2004-12-21
影响因子: 11.1
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Koh, DW;Lawler, AM;Dawson, TM
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期刊: GENE
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发表时间: 2003-04-15
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