异硫氰酸酯抑制肺癌转移作用及其分子机理研究

项目名称： 异硫氰酸酯抑制肺癌转移作用及其分子机理研究

项目编号： No.30873035

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 徐克

作者单位： 天津医科大学

项目金额： 32万元

中文摘要： 异硫氰酸酯是存在于十字花科蔬菜中的一种天然产物。在多种动物模型上的研究显示异硫氰酸酯可抑制由多种化学致癌剂诱发的癌变。最新的研究显示异硫氰酸酯具有抗癌作用，抑制多种肿瘤细胞的生长。然而，异硫氰酸酯在肿瘤转移方面的作用研究目前还很少。我们的项目发现异硫氰酸苄酯和异硫氰酸苯乙酯有效抑制肺癌细胞的转移潜能。进一步的机理研究表明，异硫氰酸苄酯和异硫氰酸苯乙酯抑制肺癌细胞增殖，抑制其迁移和侵袭能力，调控转移相关基因，诱导细胞凋亡，引起细胞周期停滞，诱发氧化损伤。细胞的AKT和MAPK信号通路受到调控。我们的研究为抗肿瘤转移开拓了新思路，同时为将异硫氰酸酯开发为抗肺癌，以致其它类型肿瘤的抗癌新药奠定了基础。 本项目组已发表论文6篇，包括SCI收录论3篇；申请了2项异硫氰酸苄酯和异硫氰酸苯乙酯作为抗癌新药的国家发明专利，其中1项已由中华人民共和国国家知识产权局授权。参加学术会议5次。

中文关键词： 异硫氰酸苄酯；异硫氰酸苯乙酯；肺癌；转移；信号通路

英文摘要： Isothiocyanates are natural compounds found in consumable cruciferous vegetables. They have been shown to inhibit chemical carcinogenesis by a wide variety of chemical carcinogens in animal models. Recent studies have also shown that isothiocyanates have antitumor activity, inhibiting the growth of several types of cultured human cancer cells. However, there are limited studies on their effects on cancer cell metastasis. In our project, we found that benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) suppress lung cancer cell metastasis potential. The mechanism study showed that BITC and PEITC inhibited lung cancer cell proliferation, migration, invasion; modulated metastasis-related genes, induced cell apoptosis, cell cycle arrest and oxidative stress. AKT and MAPK signaling pathways were involved. This may provide a novel approach for metastasis therapy of lung cancer by dietary isothiocyanates and possibly other types of cancer. We have published 6 papers on this project, 3 of them are SCI papers. We also submitted 2 patent applications on novel drug discovery; one of them has been approved by the State Intellectual Property Office of P.R.C. We attended 5 conferences.

英文关键词： benzyl isothiocyanate; phenethyl isothiocyanate; lung cnacer; metastasis;signaling pathway