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Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular
Kaifang Wang1,2, Xiaona Wang3, Minghuan Zhang3
1School of Dentistry, Shenzhen University Medical School, Shenzhen 518000, China.
Abstract:
Trichosanthin (TCS) is a type I ribosome-inactivating protein extracted from the tuberous root of the plant Trichosanthes. TCS shows promising potential in clinical drug abortion, anti-tumor and immunological regulation. However, the molecular mechanisms of its anti-tumor and immune regulation properties are still not well discovered. In the present study, we investigated the anti-tumor activity of TCS in hepatocellular carcinoma (HCC), both in vitro and in vivo. Both HCC cell lines and xenograft tumor tissues showed considerable growth inhibition after they were treated with TCS. TCS provoked caspase-mediated apoptosis in HCC cells and xenograft tumor tissues. The recruitment of CD8+ T cells to HCC tissues and the expression of chemokines, CCL2 and CCL22, were promoted upon TCS treatment. In addition, TCS induced an upregulation of Granzyme B (GrzB), TNF-α and IFN-γ in HCC tissues, which are the major cytotoxic mediators produced by T cells. Furthermore, TCS also resulted in an increase of mannose-6-phosphate receptor (M6PR), the major receptor of GrzB, in HCC tissues. In summary, these results suggest that TCS perhaps increases T-cell immunity via promoting the secretion of chemokines and accelerating the entry of GrzB to HCC cells, which highlights the potential role of TCS in anti-tumor immunotherapy.
Insights
Trichosanthin (TCS) shows anti-tumor effects in liver cancer by triggering cell death and enhancing T-cell immune responses. This suggests TCS has potential as an immunotherapy agent for hepatocellular carcinoma (HCC).
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Trichosanthin (TCS), a protein from *Trichanthes*, has potential therapeutic applications.
- The anti-tumor and immune regulatory mechanisms of TCS are not fully understood.
- Hepatocellular carcinoma (HCC) remains a significant health challenge requiring novel treatments.
Purpose of the Study:
- To investigate the anti-tumor activity of TCS in HCC.
- To elucidate the molecular mechanisms underlying TCS's effects on HCC.
- To explore TCS's potential in anti-tumor immunotherapy.
Main Methods:
- In vitro studies using HCC cell lines.
- In vivo studies using HCC xenograft models.
- Analysis of apoptosis, T-cell recruitment, chemokine expression, cytotoxic mediators, and receptor expression.
Main Results:
- TCS significantly inhibited HCC cell and tumor growth.
- TCS induced caspase-mediated apoptosis in HCC cells and tissues.
- TCS promoted CD8+ T cell recruitment and chemokine (CCL2, CCL22) expression.
- TCS upregulated cytotoxic mediators (Granzyme B, TNF-α, IFN-γ) and M6PR expression.
Conclusions:
- TCS exhibits potent anti-tumor activity against HCC.
- TCS enhances anti-tumor immunity by promoting T-cell responses and cytotoxic mediator delivery.
- TCS demonstrates significant potential as an anti-cancer immunotherapy for HCC.
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