Li Cong, Wu Xia, Zhang Honghai, Yang Gengxia, Hao Meijun, Sheng Shoupeng, Sun Yu, Long Jiang, Hu Caixia, Sun Xicai, Li Li, Zheng Jiasheng
Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
Department of Infectious Disease, the Second Affiliated Hospital of Harbin Medical University, Huanghe Road, Harbin 150081, China.
Int J Biol Macromol. 2015 Apr;75:115-20. doi: 10.1016/j.ijbiomac.2015.01.016. Epub 2015 Jan 15.
Hepatocellular carcinoma (HCC) is a highly metastatic cancer. Huaier polysaccharide (TP-1) is a naturally occurring bioactive macromolecule, found in Huaier fungus and has been shown to exert in vitro antitumor and antimetastasis for HCC, but no study has addressed in vivo efficacy and mechanisms of action. Presently, we found that TP-1 at doses of 0.5, 1 and 2mg/kg significantly inhibited tumor growth and metastasis to the lung in mice bearing HCC SMMC-7721 tumors without toxicity. The analysis of tumors by immunohistochemistry demonstrated that TP-1 inhibited PCNA expression, increased the number of TUNEL-positive cells and reduced microvessel density (MVD) to achieve this effect. Furthermore, TP-1 administration reduced the protein expression of hypoxia-inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF), AUF-1 and AEG-1, in tumor tissues. Taken together, our data suggested that the antitumor and anti-metastatic activities of TP-1 might be at least partially through down-regulation of HIF-1alpha/VEGF and AUF-1/AEG-1 signaling pathways.
肝细胞癌（HCC）是一种具有高度转移性的癌症。槐耳多糖（TP - 1）是一种天然存在的生物活性大分子，存在于槐耳真菌中，已显示出在体外对肝癌具有抗肿瘤和抗转移作用，但尚无研究探讨其体内疗效及作用机制。目前，我们发现剂量为0.5、1和2mg/kg的TP - 1可显著抑制荷HCC SMMC - 7721肿瘤小鼠的肿瘤生长和肺转移，且无毒性。通过免疫组织化学对肿瘤进行分析表明，TP - 1通过抑制PCNA表达、增加TUNEL阳性细胞数量和降低微血管密度（MVD）来实现这一效果。此外，给予TP - 1可降低肿瘤组织中缺氧诱导因子（HIF）-1α、血管内皮生长因子（VEGF）、AUF - 1和AEG - 1的蛋白表达。综上所述，我们的数据表明，TP - 1的抗肿瘤和抗转移活性可能至少部分是通过下调HIF - 1α/VEGF和AUF - 1/AEG - 1信号通路实现的。
