Effects of combined 5-Fluorouracil and ZnO NPs on human breast cancer MCF-7 Cells: P53 gene expression, Bcl-2 signaling pathway, and invasion activity

Abstract

Objective(s): The significant contribution of nanoparticles to cancer treatment has attracted therapeutic attention. The present study aimed to evaluate the synergistic effects of 5-fluorouracil (5-FU) and zinc oxide nanoparticles (ZnO NPs) as multimodal drug delivery on human breast cancer MCF-7 cells.Materials and Methods: In this in-vitro study, the impact of 5-FU and ZnO NPs in the single or combined forms was evaluated on cell viability, colony formation, apoptosis, p53 gene expression, and Bcl-2 signaling protein in MCF-7 breast cancer cell line using several techniques, such as MTT, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and Western blot.Results: In this study, 5-FU combined with ZnO NPs showed synergistic effects against MCF-7 within 48 hours. In addition, the combination of 5-FU and ZnO NPs at the respective concentrations of 1 µM and 45 µg/ml exhibited significant apoptosis (79.53%), p53 gene expression (3.6 folds), reduction of cell invasion (9.82%), and plating efficiency (5%), thereby leading to the significant reduction of cell viability (40±0.9%) and decreased Bcl-2 anti-apoptotic protein relative to untreated control cells. Conclusion: According to the results, the synergistic effects of combined ZnO NPs and 5-FU on MCF-7 human breast cancer cells were exerted via Bcl-2 inhibition and the up-regulation of p53 expression.

Keywords

• Bcl-2
• p53 expression
• Zinc oxide naoparticles
• 5-fluorouracil