Silencing Poly (ADP-Ribose) glycohydrolase (PARG) expression inhibits growth of human colon cancer cells in vitro via PI3K/Akt/NFκ-B pathway.

Abstract

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.

• Authors: Nilufer Jasmine Selimah Fauzee, Qiaozhuan Li, Ya-Lan Wang, Juan Pan
• Journal: Pathology oncology research : POR (Pathol Oncol Res) Vol. 18 Issue 2 Pg. 191-9 (Apr 2012) ISSN: 1532-2807 [Electronic] Switzerland
• PMID: 21713600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ARHGAP29 protein, human
• Elafin
• GTPase-Activating Proteins
• NF-kappa B
• PI3 protein, human
• RNA, Messenger
• Proto-Oncogene Proteins c-akt

Topics

• Apoptosis
• Blotting, Western
• Cell Cycle
• Cell Nucleus (metabolism)
• Cell Proliferation
• Colonic Neoplasms (genetics, metabolism, pathology)
• Elafin (genetics, metabolism)
• Flow Cytometry
• GTPase-Activating Proteins (antagonists & inhibitors, genetics, metabolism)
• Humans
• NF-kappa B (genetics, metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Tumor Cells, Cultured