Abstract

Background/Objectives: The reversal effect of cGAMP, as a STING pathway regulator, on oxaliplatin resistance in colorectal cancer was investigated, and its mechanism was proposed. Methods: The efficacy and mechanism of the cGAMP and oxaliplatin combination for oxaliplatin-resistant colorectal cancer through a nude mouse tumor model were investigated and analyzed, and a western blot analysis of tumors was applied. Results: The reversal effect of cGAMP on oxaliplatin resistance in colorectal cancer was investigated, and its mechanism was proposed. After OXA treatment, the IC50 values of HCT116 and HCT116/L cells were 9.04 μmol/L and 47.04 μmol/L, respectively. In nude mouse tumor models, the combination of cGAMP and oxaliplatin significantly reversed the resistance of oxaliplatin to primary drug-resistant HCT116/L colorectal cancer, and the tumor inhibition rate increased from 8% (oxaliplatin alone) to 60% (combination). In the HCT116 nude mouse transplanted tumor model, the combined treatment of cGAMP and oxaliplatin also showed a more significant tumor inhibition effect than oxaliplatin alone, and the tumor inhibition rate increased by 39%, indicating that cGAMP had a considerable improvement effect on oxaliplatin acquired resistance. These results fully demonstrated the synergistic effect of cGAMP and oxaliplatin. Western blot results showed that cGAMP enhanced the sensitivity of oxaliplatin-resistant tumor cells by down-regulating the expression of p-PI3K and p-AKT and up-regulating the expression of p53 protein. Conclusions: cGAMP, as an immunomodulator against oxaliplatin resistance, shows a potential application prospect in treating oxaliplatin-resistant colorectal cancer.