Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Nanoparticle on the MCF-7 Breast Cancer Cells and HFS Human Foreskin Cells

Abstract

Background: The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize drug efficacies. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. Objective: The study aimed to evaluate antitumor activity of the combination therapy of GEM and ATV encapsulated in nanodroplets of microemulsion (ME) formulation in MCF-7 breast cancer cells and healthy HFS human foreskin cells. Method: The physical characterization of drug formulas has been studied by the transmission electron microscope (TEM). The cytotoxicity and efficacy of the formulation were examined by 3(4,5-dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay, light microscopy, and ApopNexin apoptosis detection kit. Results: It has been found that the IC50, inhibitory concentration at which 50 percent of the cells inhibited, for the combination of GEM and ATV at 1:2 ratio, respectively, in the ME (GEM/2ATVME) with a droplet diameter of 4.81±0.86 nm, subjected into the MCF-7 cells for 24h, was similar to the combination of GEM and ATV at 1:1 ratio, respectively, in water (GEM/ATV). According to the FITC/PI assay, 5 µM of GEM/2ATV-ME was less toxic on the HFS cells as higher percentages of viable cells (85.15%) were detected when compared to the GEM/ATV that caused reduction in the percentages of the viable cells (66.45%). Conclusion: Formulating GEM with ATV in ME has improved the therapeutic anticancer potential of both drugs while reducing their side effects on the normal cells.