Lack of Metformin Effects on Different Molecular Subtypes of Breast Cancer under Normoglycemic Conditions: An in vitro Study

Background: In the past few years, a considerable number of preclinical studies have been proposed metforminas a potential anticancer agent, but some of these studies suffer from a number of methodological limitationssuch as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applyingsuprapharmacological levels of the drug. These objections have limited the translation of published preclinicaldata to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin ondifferent molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemicconditions in vitro. Materials and
Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 andtriple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM)at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbasedcytotoxicity assays were also performed with metformin alone or in combination with paclitaxel.
Results:Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell linesin the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplasticproperties of paclitaxel was apparent under the tested conditions.
Conclusions: Metformin is probablyunable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations andnormal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasmaconcentration of metformin in the clinical setting for assessment of anticancer effects i n normoglycemic patients.