The synergistic antitumour effect of Carrimycin combined with 5-fluorouracil on colorectal cancer

5-Fluorouracil (5-FU)-based chemotherapy often leads to drug resistance and adverse reactions in individuals with colorectal Cancer (CRC). Carrimycin (CAM), a drug with notable antitumour effects across various tumour types, including hepatocellular carcinoma, glioblastoma, and small-cell lung carcinoma, offers an alternative owing to its limited side effects. Combination therapy is a common strategy to mitigate the negative effects of 5-FU and enhance its therapeutic efficacy. This study aimed to investigate the potential synergistic antitumour effects of CAM and 5-FU on HCT-15 and HT-29 CRC cell lines. Using computational analysis, we identified and quantified the synergistic effects of CAM and 5-FU. The combination therapy significantly outperformed 5-FU alone in inhibiting cell proliferation, colony formation, cell cycle progression, and migration. Additionally, it markedly increased the levels of Reactive Oxygen Species and induced DNA damage. Furthermore, RNA-seq analysis revealed that the JNK and p38 MAPK signalling pathways were activated by this combination. In addition, the synergistic effects of the combination therapy were validated in a mouse subcutaneous tumour graft model. In conclusion, CAM enhances the sensitivity of CRC cells to 5-FU both in vitro and in vivo, suggesting its potential as a promising candidate for combination Cancer therapy.

Carrimycin; Cell cycle; DNA damage response; MAPK pathway; Reactive oxygen species.