The inhibitory effects of nano-encapsulated metformin on growth and hTERT expression in breast cancer cells

Abstract

Metformin has recently received attention for its potential effects with respect to cancer prevention and treatment. Nonetheless, the low bioavailability and short half-life of metformin hamper its application as an anti-cancer drug. The present study aims to evaluate the efficiency of PLGA-PEG as a nanocarrier for metformin to enhance anticancer effects. For this purpose, metformin-loaded PLGA-PEG NPs were synthetized and characterized using DLS, FE-SEM and FTIR. Then, the inhibitory effects of free and nano-encapsulated forms of metformin on growth and expression levels of hTERT in two breast cancer cell lines, T47D and MDA-MB-231, were evaluated using MTT and qPCR assays, respectively. Assessment of drug toxicity revealed that metformin-loaded NPs had more cytotoxic effects than free form in both cell lines at a dose-and time-dependent manner. The IC50s of free and nanoformulated metformin for MDA-MB-231 cells were lower than T47D cells, indicating the higher sensitivity of the triple-negative phenotype. Also, it was found that nanoformulated metformin than free metformin could further decline the expression levels of hTERT in both cell lines, especially MDA-MB-231 (p < 0.05). It is speculated that nano-encapsulation of metformin into polymeric NPs may be a promising and convenient approach to improve its efficiency in breast cancer therapy. (c) 2017 Elsevier B.V. All rights reserved.