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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590127/
• 关键词: Cordyceps sinensis; cordycepin; adenosine cleaminase inhibitor; mouse B16-B16 melanoma cells; spontaneous metastatic model; survival; マウスメラノーマB16-BL6; 高転移性がん細胞

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.

我们证明了邦迪菌素（3'-脱氧二苯胺）是培养的虫草sinensis（WECS）水提取物的活跃物质。在该项目的第一年中，我研究了使用小鼠B16-BL6黑色素瘤和Lewis Lung Carcinoma细胞WECS和Cordyceptin的抗肿瘤作用，研究了2'-脱氧霉素（DCF）（DCF）对WECS和Cordyceptin的抗肿瘤作用的可调节作用。结果，在5μM处的DCF分别增强了WEC和Cordyceptin的抗肿瘤作用，分别为三百倍和三百倍。在两种细胞系的生长曲线上，单独的DCF在5μM处完全无效。在该项目的第二年中，我们评估了WEC对赞助转移小鼠模型的抗转移效应，该模型通过用B16-BL6细胞接种到右后腿的脚垫来制备。接种两周后，完全切除了原发性肿瘤。单独使用DCF（0.05 mg/kg）或DCF加WEC（10 mg/kg），在肿瘤接种后腹膜内进行一周，在原发性肿瘤切除后的一周内延长模型小鼠的存活，而单独使用WEC（10 mg/kg）的同一范围内的终有效率的终有效率的延长了wec（10 mg/kg），则在同一范围内延长了同一范围的繁殖，该培训的效率是繁殖的。 Kaplan-Meier分析。在所有情况下，对照小鼠的生存时间均小于53天，而在110天内施用WEC（10 mg/kg）的六只小鼠中有三只。施用WECS（10 mg/kg）的小鼠均未显示出不良的全身效应。 3 mg/kg的WEC并未显示出任何抗转移作用，而100 mg/kg的WEC显着降低了小鼠的体重为不良影响。总之，在去除其无活性成分之后，WEC应该成为临床用作抗异常作用的候选者。代理人。

项目成果

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

• 发表时间: 2008
• 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

• 发表时间: 2007
• 作者: Kazuki Nakamura;et. al.;Kazuki Nakamura
• 通讯作者: Kazuki Nakamura

Potential for liver metastasis did not correlate with that for lung metastasis in a study using four different mouse melanoma cell lines

在使用四种不同小鼠黑色素瘤细胞系的研究中，肝转移的可能性与肺转移的可能性不相关

• 发表时间: 2007
• 作者: Erika Kubo;Noriko Yoshikawa;Kazuki Nakamura;et. al.
• 通讯作者: et. al.

Cordycepin,an active ingredient of Cordyceps sinensis,inhibits tumor growth by stimulating adenosine A_3 receptor

冬虫夏草活性成分虫草素通过刺激腺苷A_3受体抑制肿瘤生长

• 发表时间: 2006
• 作者: Noriko Yoshikawa;Kazuki Nakamura
• 通讯作者: Kazuki Nakamura

CORDYCEPIN AND CORDYCEPS SINENSIS REDUCE THE GROWTH OF HUMAN PROMYELOCYTIC LEUKAEMIA CELLS THROUGH THE Wnt SIGNALLING PATHWAY

• DOI: 10.1111/j.1440-1681.2007.04781.x
• 发表时间: 2007-10
• 期刊: Clinical and Experimental Pharmacology and Physiology
• 影响因子: 2.9
• 作者: N. Yoshikawa;Kazuki Nakamura;Y. Yamaguchi;S. Kagota;K. Shinozuka;M. Kunitomo