Effects of combined 5Fluorouracil and ZnO NPs on human breast cancer MCF7 Cells: P53 gene expression, Bcl2 signaling pathway, and invasion activity

Objective(s): The significant contribution of nanoparticles to cancer treatment has attracted therapeutic attention. The present study aimed to evaluate the synergistic effects of 5fluorouracil (5FU) and zinc oxide nanoparticles (ZnO NPs) as multimodal drug delivery on human breast cancer MCF7 cells.Materials and Methods: In this invitro study, the impact of 5FU and ZnO NPs in the single or combined forms was evaluated on cell viability, colony formation, apoptosis, p53 gene expression, and Bcl2 signaling protein in MCF7 breast cancer cell line using several techniques, such as MTT, clonogenic assay, flow cytometry, realtime quantitative polymerase chain reaction, and Western blot.Results: In this study, 5FU combined with ZnO NPs showed synergistic effects against MCF7 within 48 hours. In addition, the combination of 5FU 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 Bcl2 antiapoptotic protein relative to untreated control cells. Conclusion: According to the results, the synergistic effects of combined ZnO NPs and 5FU on MCF7 human breast cancer cells were exerted via Bcl2 inhibition and the upregulation of p53 expression.