MELATONIN ENHANCES TOPOTECAN SENSITIVITY IN RESISTANT SW480/TPT COLORECTAL CANCER CELLS

Background & Aims: Chemoresistance, particularly to topotecan (TPT), remains a major obstacle in colorectal cancer treatment.As a topoisomerase I inhibitor, TPT's efficacy is limited by P-glycoprotein (P-gp)-mediated drug resistance.This study examined melatonin's potential to overcome TPT resistance in SW480/TPT cells and its underlying mechanisms .Materials & Methods: SW480 and drug-resistant SW480/TPT cells were maintained in RPMI-1640/10% FBS.Cells were treated with TPT (0.1-5 M) alone or combined with melatonin (1-20 M) in serum-free medium for 48 hours.Apoptosis was quantified using the Cell Death Detection ELISA kit.MDR1 expression and P-gp levels were assessed after melatonin treatment (10 M, 48h).All experiments included 3 biological replicates, with data analyzed by one-way ANOVA.Results: Melatonin synergistically enhanced TPT efficacy, reducing the IC50 from 2.80.3 M to 0.80.1 M (71.4% reduction, p<0.001).Combination therapy increased apoptosis from 152% (TPT alone) to 454% (3-fold increase, p<0.001).Mechanistically, melatonin downregulated MDR1 expression by 655% and decreased P-gp levels by 584% versus untreated controls (p<0.001) .Conclusion: Melatonin significantly reverses TPT resistance in colorectal cancer cells by suppressing P-gp/MDR1.These findings position melatonin as a promising adjuvant for combination chemotherapy, warranting further investigation in preclinical models and clinical trials.