PI3K Inhibitor Combined with MiR-125b Inhibitor Sensitize TMZ-induced Anti-glioma Stem Cancer Effects Through Inactivation of Wnt/β-catenin Signaling Pathway

Overview

Journal In Vitro Cell Dev Biol Anim

Publisher Springer

Specialties Biology
Cell Biology

Date 2015 Jul 15

PMID 26170223

Citations 22

Authors

Lei Shi

Xifeng Fei

Zhimin Wang

Yongping You

Affiliations

Soon will be listed here.

Abstract

Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly with a high frequency. Glioblastoma stem cells (GSCs) causing resistance to drug therapy were considered to be one of the key factors. The mechanisms underlying GSCs resistance to TMZ are not fully understood. MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance. Our previous studies showed that miR-125b was necessary for GSCs fission, and inhibition of which could enhance the chemosensitivity of GSCs to TMZ. Recent studies have evidence that a variety of drugs and upstream factors work through PI3K/Akt pathway, and the effects of PI3K/Akt pathway inhibition on GSCs were much more than non-GSCs. In this study, we found that PI3K inhibitor combined with miR-125b inhibitor caused a marked increase of TMZ-induced GSC proliferation and invasiveness inhibition. To explore the potential mechanism, we found that this novel combinatorial regimen leads to changes of inactivation of Wnt/β-catenin pathway which regulates a series of cell activities including cell apoptosis, proliferation, differentiation, and metabolism. Taken together, our data strongly support an important role for PI3K inhibitor and miR-125b inhibitor on conferring GSCs resistance to TMZ through targeting Wnt/β-catenin signaling pathway.

Citing Articles

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