肉桂和川桂中抗肿瘤二萜化学成分及作用机制研究

In recent year, anti-cancer drugs from traditional Chinese medicine were given much more attention on because of its high effect and low toxicity. The latest study suggests that CYP2J2 and it metabolites EETs play an important role in promoting the proliferation of tumor cells and enhancing the metastasis, as well as inhibiting the apoptosis of cancer cells. In our early study, we found that the extraction and new skeleton diterpenoids from Cinnamomum cassia and Cinnamomum argenteum Gamble significantly inhibit activities of tumor cells in vivo and vitro, Moreover, they selectively repress the activity of CYP2J2. Our research will proceed on isolation and identification of active compounds from chloroform and n-butanol fraction of Cinnamomum cassia and Cinnamomum argenteum Gamble, which are effective on anti-tumor and CYP2J2 enzyme inhibition. In addition, we will explore the mechanism of preventing activities of CYP2J2 to effectively block tumor by these compounds. The implementation of the project will enhance the awareness of Malignant tumor, and point out the function of CYP2J2 in anti-tumor therapy. It means CYP2J2 will become potential target of anti-tumor drug via analyzing the relevance of it with the tumor. Therefore, it is of great important significance for the development of new anti-cancer medicine and control methods of tumor.

从传统中药寻找高效低毒的抗癌药物备受重视。最新研究表明，CYP2J2 及其酶活性产物 EETs具有促肿瘤细胞增殖、肿瘤转移和抑制肿瘤细胞凋亡的作用。申请者在前期实验中发现：两种樟科植物肉桂和川桂中提取物及其中新骨架二萜类成分具有显著的体内外抑瘤活性及选择性抑制CYP2J2酶活性。本研究将进行肉桂和川桂抗肿瘤与抑制CYP2J2酶活性有效部位氯仿部位和正丁醇部位活性化合物的分离及结构鉴定，并探讨活性化合物抑制CYP2J2酶活性从而具有抗肿瘤作用的机制。项目的实施将加深对人类恶性肿瘤疾病的认识，将更清晰地了解CYP2J2酶在抗肿瘤中的作用，通过分析其与肿瘤的相关性，提示CYP2J2酶作为潜在的抗肿瘤药物靶标的可能性，对进一步研究人类恶性肿瘤疾病的防治和开发新的治疗药物具有十分重要的意义。

申请者在前期实验中发现两种樟科植物肉桂和川桂中提取物及其中新骨架二萜类成分具有显著的体内外抑瘤活性。本项目对三种樟科植物肉桂，川桂，香桂次生代谢产物进行了研究，共分离得到化合物145个，新化合物48个，新骨架化合物4个，并对多种不同种类化合物进行了相应活性研究。研究表明，肉桂主要化学成分为二萜；川桂主要成分为降倍半萜；香桂主要成分为木脂素和糖苷类化合物。相关研究发表SCI论文8篇，其中影响因子大于5的论文1篇，申请并获授权专利1项。