Allicin mediated CD8+ T cell anti-colorectal cancer by targeting STAT3

Allicin has been identified as a potential drug for colorectal Cancer (CRC) therapy, whether it plays an anti-tumor effect via regulating immunity has not yet been explored. We investigated the mechanism by which allicin combated tumors in the treatment of CRC. Flow cytometry was utilized to analyze the infiltration of immune cells and the functionality of CD8⁺ T cells after treating with allicin in tumor-loaded C57BL/6 mice. To assess the unique effect of allicin on T cells, we employed male OT-I mice for the analysis. RNA-seq and WB were utilized to determine the mechanism of allicin on T cells. The proliferation and migration of HCT116 and HT29 cells were evaluated using CCK-8, cloning, and transwell assays. BALB/c-nude mice were utilized to test the anti-tumor efficacy of allicin. Allicin could significantly inhibit the tumor growth, with an inhibition rate of 72.2 %. Moreover, allicin promoted the CD8⁺T cells infiltration from 18.44 % to 47.01 % in vivo. Moreover, allicin enhanced the function of CD8⁺T cells via promoting the secretion of IL-2, TNF-α and IFN-γ, differentiation of effector T cells as well as decreasing the expression of TIM-3 in vitro. Ovalbumin-specific CD8⁺T cells were obviously increased after treating with allicin from 41.96 % to 58.40 % in vivo. Mechanically, allicin could enhance the anti-CRC function through targeting STAT3 in CD8⁺T cells and tumor cells, with an inhibition rate of 80.3 % and 53.6 %, which suggests that allicin is a promising candidate for CRC treatment.

Allicin; Anti-CRC; CD8(+)T cells; Cell differentiation; STAT3 pathway.