Cambodian Phellinus linteus inhibits experimental metastasis of melanoma cells in mice via regulation of urokinase type plasminogen activator
Cambodian Phellinus linteus inhibits experimental metastasis of melanoma cells in mice via regulation of urokinase type plasminogen activator
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DOI：
10.1248/bpb.28.27
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发表时间：
2005-01-01
影响因子：
2
通讯作者：
Kim, SH
中科院分区：
文献类型：
--
作者：
Lee, HJ;Lee, HJ;Kim, SH
桑黄(Phellinus linteus，PL)是一种主要分布于热带美洲、非洲和亚洲国家的真菌，包括韩国、日本和中国。PL传统上用于治疗关节炎、肝脏损伤和癌症。然而，对柬埔寨桑黄属物种的生物活性和特性知之甚少。因此，本研究对桑黄水提物(CPL)的抗肿瘤转移机制进行了研究。通过DNA序列分析和国家生物技术信息中心的比对，柬埔寨蘑菇被鉴定为桑黄属物种，与桑黄属的同源性为99%。CPL在1 mg/ml浓度下对B16BL6细胞和侵袭性黑色素瘤细胞无明显的细胞毒作用，但对B16BL6细胞诱导的血小板聚集有抑制作用，对B16BL6细胞与明胶的黏附和侵袭也有抑制作用，且呈浓度依赖关系。同样，CPL在50 mg/kg剂量下对B16BL6细胞静脉注射的C57BL/6小鼠肺转移集落的抑制率达55.5%，与未治疗对照组相比呈剂量依赖关系。CPL还以浓度依赖的方式下调肿瘤细胞侵袭转移关键蛋白之一尿激酶型纤溶酶原激活物(UPA)的表达，而逆转录聚合酶链式反应(RT-PCR)对基质金属蛋白酶2(NINIP-2)及其组织抑制物2(TIMP-2)的表达无明显影响。综上所述，这些发现表明，柬埔寨桑黄可能至少部分通过调节与肿瘤细胞诱导的血小板聚集(TCIPA)相关的uPA来抑制肿瘤转移，并建议进一步研究有效成分的分离和黏附分子信号通路的参与。
Phellinus linteus (PL) is a fungus mainly found in tropical America, Africa and Asian countries including Korea, Japan and China. PL has been traditionally used for the treatment of arthritis, liver damage and cancer. However, little was known on the biological activity and characterization of Phellinus species in Cambodia. Thus, in the present study, the anti-metastatic mechanism of aqueous extract of Cambodian Phellinus linteus (CPL) was evaluated. Cambodian mushroom was identified as a Phellinus species with 99 % homology of Phellinus linteus by DNA sequence analysis and comparison by the National Center for Biotechnology Information. CPL did not exhibit any significant cytotoxicity against B16BL6 cells, invasive melanoma cells at I mg/ml. However, CPL inhibited platelet aggregation induced by B16BL6 cells and also disrupted the adhesion to gelatin and invasion of B16BL6 cells in a concentration dependent manner. Similarly, CPL dose-dependently inhibited the pulmonary metastatic colonies in C57BL/6 mice intravenously injected by B16BL6 cells up to 55.5 % at a dose of 50 mg/kg compared with untreated control. CPL also down-regulated the expression of urokinase type plasminogen activator (uPA), one of key proteins associated with invasion and metastasis of tumor cells in a concentration dependent fashion, while CPL didn't significantly affect the expression of matrix metalloproteinase 2 (NINIP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) by reverse transcriptase-polymerase chain reaction (RT-PCR). Taken together, these findings indicate that Cambodian Phellinus linteus may inhibit metastasis at least partly via regulation of uPA associated with tumor cell induced platelet aggregation (TCIPA) and also suggest a further study for isolation of active ingredients and the involvement of adhesion molecule signaling pathway.