PI3K inhibitor combined with miR125b inhibitor se

Authors: Lei Shi Xifeng Fei Zhimin Wang Yongping You

Publish Date: 2015/07/14

Volume: 51, Issue: 10, Pages: 1047-1055

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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 miR125b 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 nonGSCs In this study we found that PI3K inhibitor combined with miR125b inhibitor caused a marked increase of TMZinduced GSC proliferation and invasiveness inhibition To explore the potential mechanism we found that this novel combinatorial regimen leads to changes of inactivation of Wnt/βcatenin 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 miR125b inhibitor on conferring GSCs resistance to TMZ through targeting Wnt/βcatenin signaling pathwayThis work was supported by the China Natural Science Foundation 81000963 and 81370062 Jiangsu Provinces 333 Talent Program BRA2011046 Jiangsu Province six personnel peak funded projects 2013WSN028 the Natural Science Foundation of Suzhou no SYS201307 Jiangsu Provinces Natural Science Foundation BK2012670 Medical Research Foundation by Jiangsu Province Health Department YG201301 and Z201318 the Clinical Technology Development of Jiangsu University JLY20120053 Suzhou City Xing Wei Youth Science and technology project kjxw2014059 the Kunshan Social Development Foundation KS1006 KS1009 and the Suzhou Social Development Foundation SYS201063 The funders had no role in study design data collection and analysis decision to publish or preparation of the manuscript

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