Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer.

ABSTRACT: Increasing interest in repurposing the diabetic medication metformin for cancer treatment has raised important questions about the translation of promising preclinical findings to therapeutic efficacy, especially in non-diabetic patients. A significant limitation of the findings to date is the use of supraphysiologic metformin doses and hyperglycemic conditions in vitro. Our goals were to determine the impact of hyperglycemia on metformin response and to address the applicability of metformin as a cancer therapeutic in non-diabetic patients. In normoglycemic conditions, lower concentrations of metformin were required to inhibit cell viability, while metformin treatment in hyperglycemic conditions resulted in increased glucose uptake and glycolytic flux, contributing to cell survival. Mecha

SUBMITTER: Litchfield LM 

PROVIDER: S-EPMC4695136 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature