Li Chunman, Zeng Meiqi, Chi Huju, Shen Jing, Ng Tzi-Bun, Jin Guangyi, Lu Desheng, Fan Xinmin, Xiong Bilian, Xiao Zhangang, Sha Ou
Department of Anatomy, Histology and Developmental Biology, School of Basic Medical Sciences, Shenzhen University Health Science Centre, Shenzhen, Guangdong, China.
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
Oncotarget. 2017 Apr 18;8(16):26460-26470. doi: 10.18632/oncotarget.15518.
Trichosanthin is a plant toxin belonging to the family of ribosome-inactivating proteins. It has various biological and pharmacological activities, including anti-tumor and immunoregulatory effects. In this study, we explored the potential medicinal applications of trichosanthin in cancer immunotherapy. We found that trichosanthin and cation-independent mannose-6-phosphate receptor competitively bind to the Golgi-localized, γ-ear containing and Arf-binding proteins. It in turn promotes the translocation of cation-independent mannose-6-phosphate receptor from the cytosol to the plasma membrane, which is a receptor of Granzyme B. The upregulation of this receptor on the tumor cell surface increased the cell permeability to Granzyme B, and the latter is one of the major factors of cytotoxic T lymphocyte-mediated tumor cell apoptosis. These results suggest a novel potential application of trichosanthin and shed light on its anti-tumor immunotherapy.
天花粉蛋白是一种属于核糖体失活蛋白家族的植物毒素。它具有多种生物学和药理活性，包括抗肿瘤和免疫调节作用。在本研究中，我们探索了天花粉蛋白在癌症免疫治疗中的潜在医学应用。我们发现天花粉蛋白与不依赖阳离子的甘露糖-6-磷酸受体竞争性结合高尔基体定位的、含γ-耳和Arf结合蛋白。这反过来促进了不依赖阳离子的甘露糖-6-磷酸受体从细胞质转移到质膜，而质膜是颗粒酶B的受体。肿瘤细胞表面该受体的上调增加了细胞对颗粒酶B的通透性，而颗粒酶B是细胞毒性T淋巴细胞介导的肿瘤细胞凋亡的主要因素之一。这些结果提示了天花粉蛋白的一种新的潜在应用，并为其抗肿瘤免疫治疗提供了线索。
