Oxyresveratrol Alleviates Irinotecan-Induced Diarrhea and Enhances Antitumor Effects in Colorectal Cancer

Xing Yang,1,2 Hengxiang Yu,3 Liming Zhou3 1School of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan, 637600, People’s Republic of China; 2The Fourth People’s Hospital of Nanchong, Nanchong, Sichuan, 637600, People’s Republic of China; 3West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Liming Zhou, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, No. 17 People’s South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-13032896118, Email [email protected]: To investigate whether oxyresveratrol (OXY) can alleviate irinotecan (CPT-11)-induced intestinal toxicity and whether the combination of these two drugs can enhance the inhibition of colorectal cancer cells.Methods: The CCK-8 assay was used to assess the inhibitory effects of OXY and CPT-11, both as monotherapies and in combination, on the proliferation of colorectal cancer cell lines HCT116 and SW620. Mice were grouped (8/mice/group) into: control, CPT-11, low-dose OXY+CPT-11, high-dose OXY+CPT-11. Each trial was conducted as an independent experiment. A mouse diarrhea model induced by CPT-11 was established to observe the general condition, diarrhea score, spleen and colon of each group of mice. Bioinformatics tools were employed to predict the targets of OXY and CPT-11, followed by GO and KEGG enrichment analyses.Results: CPT-11 inhibited the growth of colorectal cancer cells in a dose-dependent manner, and OXY combined treatment had additive effects. Mice in the CPT-11 group experienced significant weight loss and severe diarrhea, while the co-administration of OXY alleviated these adverse effects. Bioinformatics analysis revealed that the targets of OXY and CPT-11 were enriched in pathways such as PI3K/Akt and cell cycle, suggesting that the combination therapy might exert a synergistic effect by modulating these pathways.Conclusion: The combination of OXY and CPT-11 enhances the inhibitory effect on colorectal tumor cells and reduces the intestinal toxicity induced by CPT-11. This study provides a novel strategy for colorectal cancer chemotherapy.Keywords: oxyresveratrol, OXY, irinotecan, CPT-11, colorectal cancer