Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, China.
Pathol Oncol Res. 2012 Apr;18(2):191-9. doi: 10.1007/s12253-011-9428-1. Epub 2011 Jun 30.
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 G(0)/G(1) 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 Akt(473) 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.
聚 ADP-核糖聚合酶（PARP）与聚 ADP-核糖糖水解酶（PARG）密切相关，与后者相比，在实验和临床癌症试验中已经得到了深入研究。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）对其进行沉默。MTT 检测表明，人 Lovo 结肠癌细胞生长受到抑制，流式细胞术显示转染 Lovo 细胞中 G0/G1 期细胞群增加，S 期减少。此外，我们的结果表明，沉默 PARG 的作用导致 PARP 表达的抑制；与核因子 kappa-B（NFκ-B）表达减少和 Akt（473）磷酸化增加有关；提示磷酸肌醇 3-激酶（PI3K）/Akt/NFκ-B 通路对于细胞生长和增殖很重要。因此，本研究强调并集中于沉默 PARG 的相关性，其通过 PI3K/Akt/NFκ-B 通路抑制人结肠癌细胞的生长；因为结肠癌仍然是全世界最常见的癌症之一，具有高发病率和死亡率。
