SYNERGISTIC SUPPRESSION OF TUMOR GROWTH BY SELENOCYSTINE AND 5-FLUOROURACIL THROUGH JAK/STAT PATHWAY INHIBITION AND IMMUNE CHECKPOINT REGULATION

Background: Liver cancer remains a major clinical challenge due to its aggressive progression and resistance to conventional therapies. The JAK-STAT signaling pathway and PD-1/PD-L1 immune checkpoint axis are key contributors to tumor growth and immune evasion. Objective: This study aimed to evaluate the combined therapeutic effect of Selenium Cysteine (SeCys) and 5-Fluorouracil (5-FU) on tumor growth inhibition, immune modulation, and signaling pathway regulation in a preclinical liver cancer model. Methods: We conducted an in vivo study with 250 subjects assigned to control, SeCys, 5-FU, or combination treatment groups. Tumor volumes, survival times, JAK-STAT pathway activation (pJAK2, pSTAT3), PD-L1 expression, and immune cell infiltration (CD8⁺ T-cells) were measured. Statistical analyses included ANOVA, Kruskal–Wallis tests, t-tests, Mann–Whitney U tests, and Pearson correlation. Results: Combination therapy significantly inhibited tumor growth (mean TGI 50.82%, p < 0.0001), reduced pSTAT3 levels (χ² = 88.456, p < 0.0001), and increased PD-L1 mRNA expression (t = 8.399, p < 0.0001) compared to controls.