Evaluation of PI3K/AKT, EGFR, P53, Wee1 genes expression in cervical cancer cells induced by chitosan-cisplatin nanoparticles Enhanced with Gemcitabine
DOI:
https://doi.org/10.22034/LSSJ.2025.133Abstract
Abstract
Introductopn: Cervical cancer remains one of the leading cancers in the world and is considered one of the worst health issues affecting most developing countries. Infection by human papillomavirus induces critical cellular pathways such as PI3K/AKT, EGFR, P53, and Wee1. In the present study, the researchers investigate the effects that chitosan-cisplatin nanoparticles combined with gemcitabine will have on cervical cancer cells in the name of altering the expression of some important genes.
Materials and Methods: The current study deals with the preparation, cisplatin and gemcitabine loading on chitosan nanoparticles, cultural manipulations of a HeLa cell line and its treatment using different concentration series of nanoparticles, characterization using UV-Vis Spectroscopy, FTIR and SEM, followed by cytotoxic effects analyzed in the MTT assay and estimation of gene expressions of PI3K, AKT, EGFR, P53 and Wee1 by real time polymerase chain reaction.
Results: The prepared chitosan nanoparticles had particle sizes that ranged between 18.61 nm to 211.4 nm; besides, there was effective drug loading. The MTT assay displayed that CSNps-CP-Gem caused significant inhibition of viability, with the IC50 values calculated as 6.005 µg/mL and 4.050 µg/mL at 24 and 48 hours, respectively. Gene expression analysis showed a significant down-regulation of PI3K, AKT, and EGFR to 0.737, 0.664, and 0.578, respectively, while the P53 was upregulated two-fold to 2.274. Wee1 expression was down-regulated but not at a statistically significant level.
Discussion: These results have shown that chitosan-cisplatin nanoparticles, combined with gemcitabine, may effectively enhance the cytotoxicity to cervical cancer cells with very minimal toxicity to normal tissues. Modulation of some key signaling pathways indicates a possible mechanism for the observed therapeutic effects. The present study hence underlines the potential of nanoparticle-based drug delivery systems for the improvement of treatment outcomes in cervical cancer and thus warrants further investigation into their clinical applications.
Keywords: PI3K/AKT, EGFR, P53, Wee1 genes, cervical cancer,chitosan-cisplatin nanoparticles, gemcitabine
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