Exploring the potential of AgNPs in modulating the PI3K/AKT/mTOR pathway via miR-133a regulation in MCF-7 breast cancer cells

Document Type : Research Paper

Authors

1 Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

2 Molecular Medicine Research Center, Hamadan University of Medical Science, Hamadan, Iran

Abstract

Objective(s): Breast cancer is the most common malignancy in women. MiRNAs modulate the PI3K/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-133a 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-133a within the PAM pathway. We quantified the expression levels of miR-133a, PI3K, AKT, PTEN, and mTOR in MCF-7 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 PI3K 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-133a as a tumor suppressor in breast cancer cells remained unchanged following exposure to AgNPs (IC50).
Conclusion: The study found that AgNPs inhibit breast cancer cell growth, affecting the PAM pathway, but miR-133a remained unchanged, suggesting AgNPs may not primarily act through miR-133a. Further research is needed, but caution is advised when using AgNPs for cancer control and treatment. 

Keywords

References

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Nanomedicine Journal
Volume 11, Issue 1
January 2024
Pages 52-62

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