Evaluating the Toxicity of Doxorubicin-Silk Fibroin Nanoparticles and Its Effect on P53 Gene Expression in Breast Cancer Cell Line

Introduction: The use of drug delivery systems can increase the effectiveness of chemotherapy and reduce its side effects in the treatment of breast cancer. This study aimed to evaluate the effect of doxorubicin-containing silk fibroin nanoparticles (NF-DOX) on P53 gene expression in breast cancer cell lines and to measure its toxicity in vitro. Methods: NF-DOX was synthesized and characterized. The breast cancer cell line MCF-7 and normal HFF cell line were treated with different concentrations of NF-DOX, and its toxicity and relative expression of P53 were measured. Results: Examination and characterization of the synthesized compound of NF-DOX indicated its nanometer dimension. The drug’s cytotoxic effect on MCF-7 cells was significantly greater compared with HFF cells and the control group (P < 0.001). The IC50 values (half-maximal inhibitory concentration) for MCF-7 and HFF cells treated with NF-DOX were 229 and 647 µg/ml, respectively. The relative gene expression levels of P53 in MCF-7 and HFF cell lines compared with the controls were measured as 27.09 ± 0.51 and 0.57 ± 0.07, respectively. The relative gene expression of P53 in MCF-7 and HFF cell lines showed a significant increase (P < 0.0001) and decrease (P < 0.0006) compared with controls, respectively. Conclusion: Differential and significant changes in P53 gene expression in cell lines indicate that NF‑DOX may play an effective role in inhibition of breast cancer metastasis. The results showed a dose- and time-dependent anticancer effect of NF‑DOX, and it can be considered as a candidate for a new anticancer drug.