Metformin (MET) has received considerable attention in recent years for its anticancer potential activities. However, short half-life and weak bioavailability of MET limited its use as a chemotherapeutic agent. The present study is intended to evaluate the efficiency of PLGA-PEG as a nano-carrier for MET to increase anticancer effects on SKOV3 ovarian carcinoma cells. MET-loaded PLGA-PEG nanoparticles (NPs) were characterized through Dynamic Light Scattering (DLS), Fourier-transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FE-SEM). Anti-proliferative and apoptotic effects of nanoformulated MET were evaluated using MTT and flow-cytometric assays, respectively. Also, real-time polymerase chain reaction (Real-Time PCR) was used to determine the gene expression levels of apoptotic genes, p53 and hTERT. Evaluation of cytotoxicity showed that MET-NPs had more cytotoxicity than free MET in a time-and dose-dependent manner. The nuclei fragmentation and the percentage of apoptotic cells induced by MET-NPs were significantly higher than free MET. Also, it was found that MET-NPs triggered more cell cycle arrest at sub-G1 checkpoint than free MET. Compared to MET treated cells, the mRNA expression levels of apoptotic genes, as well as p53 and hTERT were significantly altered in MET-NPs treated cells. In conclusion, it is supposed that nano-encapsulation of MET into polymeric PLGA-PEG NPs may be a convenient drug delivery system to enhance its anticancer effects for ovarian cancer therapy.
The results provide evidence that synergistic antiproliferative effects of MET and SIL, linking to the down-regulation of Cyclin D1 and hTERT genes, and propose that MET+SIL may have therapeutic value in breast cancer therapy.
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