Mechanism of the combined action of green tea polyphenols and concurrent radiochemotherapy in regulating GSK-3beta to treat non-small cell lung cancer through the Wnt/beta-catenin pathway

Vol. 65 No. 3, 2024

ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Kebei Xie, Yanli Wang, Zimin Chen

Green tea, derived from Camellia sinensis, contains polyphenolic active compounds that exhibit diverse pharmacological effects including anticancer, anti-inflammatory, antioxidant, and immunomodulatory properties. Employing various concentrations of green tea polyphenols (GTPs; 0, 100, 200, 300, 400, 500 micro-g/mL), human normal lung epithelial cells (BEAS-2B) and non-small cell lung cancer (NSCLC) cells (A549) underwent treatment. The cell viability was assessed using the cell counting kit-8 (CCK-8) assay, proliferation was examined through the colony formation assay, apoptosis was monitored via flow cytometry, cell migration, and epithelial-mesenchymal transition (EMT)-associated proteins (E-cadherin, N-cadherin) were determined by Western blot. A549 cells were subjected to Cisplatin (0, 0.5, 1, 1.5 microM) and X-ray irradiation (0, 2, 4, 6 Gy) for treatment to probe the influence of GTPs on A549 cells in response to chemoradiotherapy. The functioning mechanism of GTPs in the context of NSCLC was validated using lithium chloride (LiCl) [a glycogen synthase kinase-3 beta (GSK-3beta) inhibitor], which activates the Wnt/beta-catenin pathway. GTPs suppressed NSCLC cell viability in a concentration-dependent pattern, with a half-maximal inhibitory concentration (IC50) of 362.5 micro-g/mL, while showing little impact on BEAS-2B cells viability (at concentrations not exceeding 500 micro-g/mL). Treatment with GTPs dampened colony formation of NSCLC cells, while promoting apoptosis. LiCl treatment vigorously attenuated the inhibitory impact of GTPs on the malignant phenotype of NSCLC cells. Mechanistic studies suggested that GTPs strengthened GSK-3beta stability, thereby impeding the Wnt/beta-catenin pathway. Tea polyphenols (TPs) in conjunction with concurrent radiochemotherapy (CRCT) enhance the stability of GSK-3beta and dampen the Wnt/beta-catenin pathway, hence exerting anticancer effects in NSCLC.

Corresponding author: Zimin Chen, MD; e-mail: ziminchen653@outlook.com

DOI: 10.47162/RJME.65.3.12 Download PDF
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