Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma

被引:4
作者
Wang, Kaifang [1 ,2 ]
Wang, Xiaona [3 ]
Zhang, Minghuan [3 ]
Ying, Zhenguang [1 ]
Zhu, Zeyao [4 ]
Tam, Kin Yip [5 ]
Li, Chunman [6 ]
Zhou, Guowei [3 ]
Gao, Feng [1 ]
Zeng, Meiqi [1 ]
Sze, Stephen Cho Wing [2 ]
Wang, Xia [3 ]
Sha, Ou [1 ]
机构
[1] Shenzhen Univ, Sch Dent, Med Sch, Shenzhen 518000, Peoples R China
[2] Hong Kong Baptist Univ, Fac Sci, Dept Biol, Hongkong 999077, Peoples R China
[3] Shenzhen Univ, Sch Basic Med Sci, Dept Anat & Histol, Med Sch, Shenzhen 518000, Peoples R China
[4] Southern Univ Sci & Technol, Sch Life Sci, Dept Biol, Shenzhen 518000, Peoples R China
[5] Univ Macau, Fac Hlth Sci, Macau, Peoples R China
[6] Shantou Univ, Guangdong Prov Key Lab Infect Dis & Mol Immunopath, Med Coll, Shantou, Peoples R China
基金
中国国家自然科学基金;
关键词
Trichosanthin (TCS); hepatocellular carcinoma (HCC); T cell; chemokine; Granzyme B (GrzB); apoptosis; INDUCED APOPTOSIS; DENDRITIC CELLS; PRODRUG-LIKE; CANCER; ACTIVATION; INFILTRATION; EXPRESSION; AUTOPHAGY; DELIVERY; PATHWAY;
D O I
10.3390/ijms24021416
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-alpha and IFN-gamma 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.
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页数:17
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