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Gold Nanocomplex Strongly Modulates the PI3K/Akt Pathway and Other Pathways in MCF-7 Breast Cancer Cell Line
Nouf N Mahmoud1, Duaa Abuarqoub2,3, Rand Zaza2
1Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
Abstract:
Conjugating drugs with gold nanoparticles (GNP) is a key strategy in cancer therapy. Herein, the potential inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, and other pathways of the MCF-7 cell-line, was investigated upon treatment with gold nanorods (GNR) conjugated with a PI3K inhibitor drug. The results revealed that the coupling of GNR with the drug drastically modulated the expression of PI3Kα at the gene and protein levels compared to the drug or GNR alone. The PI3Kα pathway is involved in tumor progression and development through the mediation of different mechanisms such as apoptosis, proliferation, and DNA damage. Treatment with the nanocomplex significantly affected the gene expression of several transcription factors responsible for cell growth and proliferation, apoptotic pathways, and cell cycle arrest. Furthermore, the gene expression of different regulatory proteins involved in cancer progression and immune responses were significantly modified upon treatment with the nanocomplex compared to the free drug or GNR alone.
Insights
Gold nanorods conjugated with a PI3K inhibitor drug effectively modulated cancer cell pathways. This novel nanocomplex significantly impacted gene and protein expression related to tumor growth and apoptosis.
Area of Science:
- Nanomedicine
- Cancer Therapeutics
- Molecular Biology
Background:
- Conjugating drugs with gold nanoparticles (GNP) is a promising strategy in cancer therapy.
- The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is crucial in tumor progression, regulating apoptosis, proliferation, and DNA damage.
Purpose of the Study:
- To investigate the inhibition of the PI3K/Akt pathway and other signaling pathways in MCF-7 cells using gold nanorods (GNR) conjugated with a PI3K inhibitor.
- To evaluate the effects of the drug-GNR nanocomplex on gene and protein expression compared to the free drug or GNR alone.
Main Methods:
- Conjugation of a PI3K inhibitor drug with gold nanorods (GNR).
- Treatment of MCF-7 cell lines with the drug-GNR nanocomplex, free drug, or GNR alone.
- Analysis of gene and protein expression levels, focusing on PI3Kα, transcription factors, apoptotic pathways, cell cycle regulators, and immune response proteins.
Main Results:
- The GNR-drug conjugate significantly modulated PI3Kα expression at both gene and protein levels compared to individual components.
- The nanocomplex treatment substantially altered the gene expression of transcription factors involved in cell growth, proliferation, apoptosis, and cell cycle arrest.
- Significant modifications in the gene expression of regulatory proteins associated with cancer progression and immune responses were observed with the nanocomplex.
Conclusions:
- Drug-conjugated gold nanorods represent a potent strategy for modulating key cancer-related pathways.
- The developed nanocomplex shows significant potential in inhibiting cancer cell growth, inducing apoptosis, and influencing immune responses.
- This approach offers a promising platform for developing targeted cancer therapies with enhanced efficacy.
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