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Development of a clinical application of Cordyceps sinensis as an antimetastatic agent utilizing the properties of its active ingredient

利用冬虫夏草活性成分的特性开发其作为抗转移剂的临床应用

基本信息

批准号：
18590127
负责人：
NAKAMURA Kazuki
金额：
$ 1.79万
依托单位：
Mukogawa Women's University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

We demonstrated that cordycepin (3'-deoxyadenosine) is an active ingredient of water extracts of the fruiting bodies of cultured Cordyceps sinensis (WECS). In the first year of this project, I investigated the adjuvant effect of 2'-deoxycoformycin (DCF), an adenosine deaminase inhibitor, on the antitumor actions of WECS and cordycepin using mouse B16-BL6 melanoma and Lewis lung carcinoma cells in vitro. As a result, DCF at 5 μM reinforced the antitumor effect of WECS and cordycepin, three and three hundred-fold, respectively. DCF alone at 5 μM was wholly ineffective on the growth curves of both cell lines. In the second year of this project, we evaluated the antimetastatic effect of WECS on a spontaneous metastatic mouse model, prepared by inoculation with B16-BL6 cells into the footpad of the right hind leg. Two weeks after inoculation, the primary tumor was completely resected. DCF (0.05 mg/kg) alone or DCF plus WECS (10 mg/kg) administered intraperitoneally for one week after tumor inoculation and for one week after primary tumor resection did not prolong the survival of model mice, while WECS (10 mg/kg) alone administered intraperitoneally for the same, duration significantly prolonged mouse survival compared with that of control mice, as shown on Kaplan-Meier analysis. Survival time of control mice was less than 53 days in all cases, while three of six mice that were administered WECS (10 mg/kg) survived over 110 days. None of the mice administered WECS (10 mg/kg) showed adverse systemic effects. WECS at 3 mg/kg did not show any antimetastatic action, while WECS at 100 mg/kg significantly reduced the body weights of mice as an adverse effect. In conclusion, after removing its inactive components, WECS should be a candidate for clinical use as an antimetastatic agent.

我们证明了虫草素（3 '-脱氧腺苷）是人工培养的冬虫夏草子实体（WECS）的水提取物的活性成分。在本项目的第一年，我使用小鼠B16-BL 6黑色素瘤和刘易斯肺癌细胞在体外研究了腺苷脱氨酶抑制剂2 '-脱氧共福霉素（DCF）对WECS和虫草素抗肿瘤作用的辅助作用。结果，5 μM的DCF分别增强WECS和虫草素的抗肿瘤作用3倍和300倍。5 μM的DCF单独对两种细胞系的生长曲线完全无效。在该项目的第二年，我们评估了WECS对自发转移小鼠模型的抗转移作用，该模型通过将B16-BL 6细胞接种到右后腿的足垫中制备。接种后两周，原发肿瘤被完全切除。如Kaplan-Meier分析所示，在肿瘤接种后一周和原发性肿瘤切除后一周，单独DCF（0.05 mg/kg）或DCF + WECS（10 mg/kg）腹腔内给药没有延长模型小鼠的存活，而WECS（10 mg/kg）单独腹腔内给药相同的持续时间与对照小鼠相比显著延长小鼠存活。在所有情况下，对照小鼠的存活时间均小于53天，而给予WECS（10 mg/kg）的6只小鼠中有3只存活超过110天。给予WECS（10 mg/kg）的小鼠均未显示出不良全身效应。3 mg/kg的WECS没有显示出任何抗转移作用，而100 mg/kg的WECS作为副作用显著降低了小鼠的体重。总之，在去除其非活性成分后，WECS应该是临床上用作抗转移剂的候选者。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

4種のマウスメラノーマ細胞における転移先臓器指向性の違いについて

四种小鼠黑色素瘤细胞转移器官趋向性的差异

DOI：
发表时间：
2008
期刊：
影响因子：
0
作者：
Namie Nejime;Noriko Yoshikawa;Noriko Yoshikawa;Noriko Yoshikawa;久保えり香;吉川紀子;久保えり香;Noriko Yoshikawa;Noriko Yoshikawa;吉川紀子;吉川紀子;禰占奈美江;久保えり香
通讯作者：
久保えり香

Cordycepin(3'-deoxyadenosine)reduces the growth of B 16-BL6 mouse melanomacells through the adenosine A_3 receptor followed by Wnt signaling pathway

虫草素（3-脱氧腺苷）通过腺苷 A_3 受体和 Wnt 信号通路减少 B 16-BL6 小鼠黑色素瘤细胞的生长