Knockdown ofAKT3(PKBγ) andPI3KCASuppresses Cell Viability and Proliferation and Induces the Apoptosis of Glioblastoma Multiforme T98G Cells

Autor: Aleksander Owczarek, Renata Suchanek, Malgorzata Kowalczyk, Grzegorz Machnik, Adam Pudełko, Anna Fila-Danilow, Monika Paul-Samojedny, Paulina Borkowska, Jan Kowalski
Rok vydání: 2014
Předmět:
Zdroj: BioMed Research International, Vol 2014 (2014)
BioMed Research International
ISSN: 2314-6141
2314-6133
DOI: 10.1155/2014/768181
Popis: Glioblastoma multiforme (GBM) is the most malignant and invasive human brain tumor that is difficult to treat and has a very poor prognosis. Thus, new therapeutic strategies that target GBM are urgently needed. The PI3K/AKT/PTEN signaling pathway is frequently deregulated in a wide range of cancers. The present study was designed to examine the inhibitory effect ofAKT3orPI3KCAsiRNAs on GBM cell growth, viability, and proliferation.T98G cells were transfected withAKT3and/orPI3KCAsiRNAs. AKT3 and PI3KCA protein-positive cells were identified using FC and Western blotting. The influence of specific siRNAs on T98G cell viability, proliferation, cell cycle, and apoptosis was evaluated as well using FC. Alterations in the mRNA expression ofAKT3,PI3KCA, and apoptosis-related genes were analyzed using QRT-PCR. Knockdown ofAKT3and/orPI3KCAgenes in T98G cells led to a significant reduction in cell viability, the accumulation of subG1-phase cells and, a reduced fraction of cells in the S and G2/M phases. Additionally, statistically significant differences in the BAX/BCL-2 ratio and an increased percentage of apoptotic cells were found. The siRNA-inducedAKT3andPI3KCAmRNA knockdown may offer a novel therapeutic strategy to control the growth of human GBM cells.
Databáze: OpenAIRE