Abstract
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 of AKT3 or PI3KCA siRNAs on GBM cell growth, viability, and proliferation.T98G cells were transfected with AKT3 and/or PI3KCA siRNAs. 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 of AKT3, PI3KCA, and apoptosis-related genes were analyzed using QRT-PCR. Knockdown of AKT3 and/or PI3KCA genes 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-induced AKT3 and PI3KCA mRNA knockdown may offer a novel therapeutic strategy to control the growth of human GBM cells.
Highlights
IntroductionChemotherapy is the most common therapeutic approach that is used to treat various cancers, but many patients with different cancers (e.g., glioblastoma multiforme) develop chemoresistance
Chemotherapy is the most common therapeutic approach that is used to treat various cancers, but many patients with different cancers develop chemoresistance
We found significantly lower mRNA levels of both AKT3 and PI3KCA in the transfected cells compared to the untransfected cells (Figures 2(a) and 2(b))
Summary
Chemotherapy is the most common therapeutic approach that is used to treat various cancers, but many patients with different cancers (e.g., glioblastoma multiforme) develop chemoresistance. Glioblastoma multiforme (GBM; WHO grade IV) is the most common malignant central nervous system (CNS) tumor and is the most aggressive form of human astrocytoma [1, 2] with a poor survival rate (approximately 15 months in patients with newly diagnosed cancers regardless of their treatment methods) [3]. The PI3 K/AKT pathway, which is an important factor for cell proliferation, growth, survival, invasiveness, and radiation resistance, is critical in the malignant phenotype of GBM [4]. Among the various survival pathways, the PI3K/AKT signaling pathway is often found to be active and plays an important role in the development of GBM
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