Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China; Drug Safety Evaluation Center, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
Toxicol Appl Pharmacol. 2018 Dec 1;360:1-8. doi: 10.1016/j.taap.2018.09.019. Epub 2018 Sep 18.
Selenium supplementation can be used to treat tumors. However, inorganic selenium is highly toxic, and natural organic selenium is extremely rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is a polysaccharide that has been approved as an anti-cancer drug in Japan and China.
Lentinan, an antitumor polysaccharide extracted from Lentinus edodes, was conjugated with seleninic acid to be transformed into ester (Se-lentinan) and utilized as drug carrier. The enhancement of the anti-tumor effects of Se-lentinan was evaluated by cell viability, cell cycle, migration, and transwell assays and animal xenograft models. The effects of Se-lentinan on the expression levels of epithelial-mesenchymal transition (EMT) markers were determined through immunofluorescence, Western blot, and immunohistochemistry analyses.
Se-lentinan inhibited the invasiveness of B16-BL6 and HCT-8 cells by suppressing EMT. In vivo, Se-lentinan significantly inhibited tumor growth and metastasis of the transplanted melanoma and colon cancer cells and showed less toxicity than sodium selenite. Moreover, Se-lentinan reduced the accumulation of selenium in the liver and kidney tissues of mice and exhibited low organ toxicity.
The antitumor activity of selenium was enhanced greatly, and its side effects were reduced with the use of lentinan as drug carrier.
硒补充剂可用于治疗肿瘤。然而，无机硒毒性很高，而天然有机硒极为罕见。多糖可以提高药物的生物利用度和靶向性。香菇多糖已在日本和中国被批准为抗癌药物。
香菇多糖是从香菇中提取的一种抗肿瘤多糖，与亚硒酸反应生成酯（Se-香菇多糖），用作药物载体。通过细胞活力、细胞周期、迁移和 Transwell 测定以及动物异种移植模型来评估 Se-香菇多糖对肿瘤的抑制作用。通过免疫荧光、Western blot 和免疫组织化学分析来确定 Se-香菇多糖对上皮间质转化（EMT）标志物表达水平的影响。
Se-香菇多糖通过抑制 EMT 抑制了 B16-BL6 和 HCT-8 细胞的侵袭性。在体内，Se-香菇多糖显著抑制了移植的黑色素瘤和结肠癌细胞的肿瘤生长和转移，且毒性低于亚硒酸钠。此外，Se-香菇多糖降低了小鼠肝、肾组织中硒的积累，表现出较低的器官毒性。
使用香菇多糖作为药物载体，大大增强了硒的抗肿瘤活性，降低了其副作用。
