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Allicin mediated CD8+ T cell anti-colorectal cancer by targeting STAT3
Dandan Guo1, Aifang Li1, Baiyan Wang1
1Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China; Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou 450046, China.
Abstract:
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.
Insights
Allicin significantly inhibits colorectal cancer (CRC) growth by boosting CD8+ T cell immunity. This natural compound targets STAT3 in immune and tumor cells, offering a promising therapeutic strategy for CRC.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide.
- Allicin, a compound found in garlic, shows potential for cancer therapy.
- The immunomodulatory effects of allicin in CRC treatment are not fully understood.
Purpose of the Study:
- To investigate the anti-tumor mechanisms of allicin in colorectal cancer.
- To determine if allicin exerts its effects by regulating the immune system, particularly CD8+ T cells.
- To elucidate the molecular targets of allicin in CRC treatment.
Main Methods:
- Flow cytometry to analyze immune cell infiltration and CD8+ T cell function in tumor-bearing mice.
- RNA-sequencing and Western blotting to identify allicin's molecular mechanisms.
- Cell proliferation, migration assays (CCK-8, cloning, transwell), and in vivo efficacy studies in nude mice.
Main Results:
- Allicin significantly inhibited tumor growth in vivo (72.2% inhibition rate).
- Allicin promoted CD8+ T cell infiltration (18.44% to 47.01%) and enhanced their function (increased IL-2, TNF-α, IFN-γ secretion; decreased TIM-3 expression).
- Allicin targeted STAT3 in CD8+ T cells and tumor cells, leading to significant anti-tumor effects (80.3% and 53.6% inhibition, respectively).
Conclusions:
- Allicin demonstrates potent anti-tumor efficacy against colorectal cancer.
- Allicin enhances anti-tumor immunity by modulating CD8+ T cell responses.
- Targeting STAT3 in both immune and tumor cells is a key mechanism for allicin's anti-CRC activity, positioning it as a promising therapeutic candidate.
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