The effect of gold nanoparticles functionalized with resveratrol (SRT501) on inhibiting STAT3 signaling and changes in the expression of MMP2 and Twist1 genes in non-small cell lung cancer
Subject Areas : Biotechnological Journal of Environmental Microbiology
1 - Department of Cell and Molecular Biology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran
Keywords: Signaling pathway, lung cancer, gold nanoparticles, RES-AuNPs, metastasis,
Abstract :
Lung cancer is the world’s second most common and deadliest cancer, distinguished by genetic and epigenetic changes, altered non-coding RNAs, and mutations in cellular signaling pathways. As traditional treatments face limitations, new therapeutic approaches are under investigation. Gold nanoparticles have emerged as promising candidates due to their efficient drug delivery properties and the ability to be functionalized with bioactive molecules. This study explored the therapeutic potential of gold nanoparticles functionalized with resveratrol extract (RES-AuNPs) for targeting non-small cell lung cancer (NSCLC) cells.The research had two primary objectives: to assess the cytotoxic effects of RES-AuNPs on A549 lung cancer cells compared to normal human dermal fibroblasts (HDF), and to examine the influence of these nanoparticles on the expression of genes related to metastasis. The synthesized RES-AuNPs were characterized using a range of analytical techniques, including FT-IR, UV-Vis spectroscopy, DLS, XRD, EDX, and TEM. Biological assays such as MTT for cell viability, flow cytometry for apoptosis, and qRT-PCR for gene expression were performed on both treated and control groups.The results showed that RES-AuNPs were more toxic to A549 cancer cells than to normal HDF cells, requiring lower concentrations to inhibit cancer cell growth. Hoechst staining confirmed apoptosis induction in cancer cells, while ROS analysis indicated higher cytotoxicity in cancer cells compared to normal cells. Additionally, RES-AuNPs significantly reduced colony formation in soft agar, suggesting suppressed cancer cell proliferation. Cell cycle analysis revealed a decrease in G1 and S phases and accumulation in G2/M, indicating cell cycle arrest. Gene expression studies demonstrated that RES-AuNPs downregulated key metastasis-related genes, especially Twist1.Overall, these findings suggest that resveratrol-functionalized gold nanoparticles could offer a promising new approach for lung cancer therapy and metastasis prevention.
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