Over the last six decades, metformin has become one of the most widely prescribed oral medications for type II diabetes. It has recently received considerable attention because of its potential role in reducing the risk of cancer development and its antineoplastic properties. However, the mechanism behind the growth-inhibitory effect of metformin on breast cancer cells remains unclear, with little consensus on which tumour subtypes benefit from treatment. Furthermore, it should be noted that much of the in vitro work published to date has used drug concentrations greatly exceeding the recommended clinical dose, and therefore may not translate directly into clinical practice.
Non-tumorigenic (MCF10A), pre-malignant (MCF10AT), pre-invasive (DCIS), the three-invasive breast cancer [MCF7, T47D and MDA-MB-231] and the fully bone-homed variant of MDA-MB-231(BM) were treated with metformin and effects on cellular proliferation were evaluated by trypan-blue exclusion and clonogenic assays. The expression levels of metformin transporters mRNA and proteins (OCT1-3, MATE1-2 and PMAT) were evaluated by qRT-PCR, western blot.
The growth-curtailing effect of metformin was achieved at 0.3mM for MDA-MB-231(P = 0.0198) in cell counting assays. Colony-forming capacity was inhibited in all cell lines tested at 0.03mM, (P
Clinically relevant doses of metformin inhibited the proliferation and colony formation of different breast cancer subtypes regardless of their receptor status and aggressiveness, including the hard to treat triple negative subtype MDA-MB-231 cells. Expression of various influx and efflux metformin-transporters is essential for cellular response and sensitivity to treatment.
Clinical trial identification
Legal entity responsible for the study
Libyan higher ministry of education
All authors have declared no conflicts of interest.