A polysaccharide from mushroom Huaier retards human hepatocellular carcinoma growth, angiogenesis, and metastasis in nude mice
A polysaccharide from mushroom Huaier retards human hepatocellular carcinoma growth, angiogenesis, and metastasis in nude mice
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DOI：
10.1007/s13277-014-2923-8
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发表时间：
2015-04-01
期刊：
影响因子：
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通讯作者：
Wang, Yihua
中科院分区：
文献类型：
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作者：
Zou, Yanmei;Xiong, Hua;Wang, Yihua
香菇怀尔已成为治疗肝细胞癌（HCC）的研究热点。目前，我们从这种蘑菇中分离纯化了一种多糖。本研究旨在探讨SP1在肝癌异种移植模型中对肿瘤生长和转移的影响，并探讨其可能的作用机制。我们的研究结果表明，SP1在0 ~ 800 μ g/ml的浓度范围内，不仅能显著抑制SMMC-7721细胞的体外增殖，而且在30mg /kg、60mg /kg和120mg /kg的剂量范围内，SP1还能抑制携带SMMC-7721小鼠的肝癌肿瘤生长和肺转移结节。同时，肿瘤组织的免疫组化分析发现，三次剂量的SP1显著抑制了体内癌细胞的增殖和微血管密度（MVD）的形成，增殖细胞核抗原（PCNA）和CD34的表达较低，但增加了末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）阳性细胞的百分比。与此观察结果一致，SP1处理降低了血清基质金属蛋白酶（MMP） 2和血管内皮生长因子（VEGF）水平，下调了缺氧诱导因子(HIF)-1 α、VEGF、MMP2、bcl-2、N-cadherin、信号传导和转录激活因子3 （STAT3）、metadherin （MTDH）的蛋白表达，上调了肿瘤组织中bax和NE-cadherin的蛋白表达。综上所述，我们的数据表明SP1似乎是一种很有希望的化学预防药物，用于HCC患者的肿瘤发生和转移，特别是在晚期。
Mushroom Huaier has become a focus of interest in the treatment of hepatocellular carcinoma (HCC). Presently, we isolated and purified one polysaccharide from this mushroom. This study aimed to investigate the effects of SP1 on tumor growth and metastasis in a HCC xenograft model and explore its possible mechanism of action. Our results showed that SP1 not only significantly inhibited the proliferation of SMMC-7721 cells in vitro at the concentration ranging from0 to 800 mu g/ml but also suppressed the HCC tumor growth and metastatic nodules to the lung in SMMC-7721-bearing mice by oral administration at three doses of 30, 60, and 120 mg/kg. Concomitantly, immunohistochemistry analysis of tumor tissues identified that SP1 administration at three doses significantly inhibited the in vivo cancer cell proliferation and microvessel density (MVD) formation, evidenced by a low proliferating cell nuclear antigen (PCNA) and CD34 expression, but increased the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells. Keeping in line with this observation, SP1 treatment decreased serum matrix metalloproteinase (MMP) 2 and vascular endothelial growth factor (VEGF) levels, downregulated the protein expression of hypoxia-inducible factor (HIF)-1alpha, VEGF, MMP2, bcl-2, N-cadherin, signal transducer and activator of transcription 3 (STAT3), and metadherin (MTDH), and upregulated bax and NE-cadherin protein expression in tumor tissues. Taken together, our data suggest that SP1 appears to be a promising chemopreventive agent for the tumorigenesis and metastasis in patients with HCC, especially at advanced stages.