Exploring the potential of AgNPs in modulating the PI۳K/AKT/mTOR pathway via miR-۱۳۳a regulation in MCF-۷ breast cancer cells

Objective(s): Breast cancer is the most common malignancy in women. MiRNAs modulate the PI۳K/AKT/mTOR (PAM) pathway, functioning as either tumor suppressors or oncogenes. This research explores the impact of AgNPs on breast cancer cells while emphasizing the interplay between miR-۱۳۳a and the PAM pathway and uncovering regulatory mechanisms.Materials and Methods: To assess the impact of AgNPs on cell growth and survival, we performed an MTT assay. Additionally, we employed bioinformatic methodologies to predict potential targets of miR-۱۳۳a within the PAM pathway. We quantified the expression levels of miR-۱۳۳a, PI۳K, AKT, PTEN, and mTOR in MCF-۷ cells after exposure to AgNPs using qRT-PCR. Furthermore, we employed Western blotting to evaluate the protein expression of mTOR.Results: The MTT assay results demonstrated a significant dose- and time-dependent inhibition of breast cancer cells by AgNPs. The qRT-PCR analysis revealed an upregulation in the mRNA expression levels of PI۳K and AKT, accompanied by a downregulation in the mRNA expression levels of PTEN and mTOR upon exposure to AgNPs. However, the efficacy and expression level of miR-۱۳۳a as a tumor suppressor in breast cancer cells remained unchanged following exposure to AgNPs (IC۵۰).Conclusion: The study found that AgNPs inhibit breast cancer cell growth, affecting the PAM pathway, but miR-۱۳۳a remained unchanged, suggesting AgNPs may not primarily act through miR-۱۳۳a. Further research is needed, but caution is advised when using AgNPs for cancer control and treatment.

کلیدواژه ها:

Breast neoplasms ، microRNAs ، Nanoparticles ، Phosphatidylinositol ۳-kinases