Lactic acidosis induces resistance to the pan-Akt inhibitor uprosertib in colon cancer cells.

ABSTRACT:

Background

Akt signalling regulates glycolysis and drives the Warburg effect in cancer, thus decreased glucose utilisation is a pharmacodynamic marker of Akt inhibition. However, cancer cells can utilise alternative nutrients to glucose for energy such as lactate, which is often elevated in tumours together with increased acidity. We therefore hypothesised that lactic acidosis may confer resistance to Akt inhibition.

Methods

The effect of the pan-Akt inhibitor uprosertib (GSK2141795), on HCT116 and LS174T colon cancer cells was evaluated in the presence and absence of lactic acid in vitro. Expression of downstream Akt signalling proteins was determined using a phosphokinase array and immunoblotting. Metabolism was assessed using ¹H nuclear magnetic resonance spect

SUBMITTER: Barnes EME 

PROVIDER: S-EPMC7188671 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature