Regulation of O2 consumption by the PI3K and mTOR pathways contributes to tumor hypoxia.

ABSTRACT:

Background

Inhibitors of the phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathway are currently in clinical trials. In addition to antiproliferative and proapoptotic effects, these agents also diminish tumor hypoxia. Since hypoxia is a major cause of resistance to radiotherapy, we sought to understand how it is regulated by PI3K/mTOR inhibition.

Methods

Whole cell, mitochondrial, coupled and uncoupled oxygen consumption were measured in cancer cells after inhibition of PI3K (Class I) and mTOR by pharmacological means or by RNAi. Mitochondrial composition was assessed by immunoblotting. Hypoxia was measured in spheroids, in tumor xenografts and predicted with mathematical modeling.

Results

Inhibition of PI3K and mTOR reduced oxygen

SUBMITTER: Kelly CJ 

PROVIDER: S-EPMC4070024 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature