豆腐柴中抗肿瘤二萜活性成分及抑制肿瘤浸润转移的作用机制研究

Angiogenesis is the propelling force for ovarian tumor growth, invasion and metastasis, hence new vessels of tumor have become the new targets of anti ovarian cancer drugs. The latest study suggests that Smad4 plays an important role in the process of ovarian tumor growth, invasion and metastasis, which is specificity target of anti-tumor drugs screening. In our early study, we found that the extraction and new diterpenoids from Premna microphylla Turcz. significantly inhibit activities of tumor cells and selectively up regulate the activity of Smad4. Moreovere, one of these compounds can block tumor invasion and metastasis by increasing of Smad4 activity. Our research will proceed on isolation and identification of active compounds from Premna microphylla Turcz.. Furthermore, we will explore the mechanism of preventing angiogenesis to effectively block tumor invasion and metastasis by these compounds. In our project, Smad4 as specificity target of anti-tumor drugs will become potential molecular markers of tumor metastasis, which will point out the function of Smad4 for inhibiting Angiogenesis and tumor invasion and metastasis. On this basis, we will improve the theory of ALK5/Smad2-Smad3-Smad4 pathways. Therefore, it is of great important significance for the development of new anti-cancer medicine.

卵巢癌的新生血管对肿瘤的生长浸润和转移具有重要意义，靶向新生血管的治疗药物是卵巢癌治疗领域的全新热点。最新研究表明，Smad4在卵巢癌肿瘤血管生长，抗肿瘤浸润转移中具有重要作用，是筛选合理抗肿瘤治疗药物的特异性靶点。申请者在前期实验中发现：豆腐柴（Premna microphylla Turcz.）提取物及其中新的二萜类成分具有显著的抑瘤活性及上调Smad4活性，其中一化合物能有效地通过上调Smad4活性而具有抗肿瘤浸润转移能力。本研究将进行豆腐柴活性化合物的分离及结构鉴定，并探讨活性化合物抑制抑瘤血管生长，抗肿瘤浸润转移作用机制。本项目可为开发全新的抗肿瘤创新药物，为Smad4 作为抗肿瘤药物特异性靶标，为Smad4作为肿瘤转移标记物等打下基础；有望展现Smad4在卵巢癌肿瘤血管生长，抗肿瘤浸润转移中的作用，进一步完善ALK5/Smad2-Smad3-Smad4通路理论。

马鞭草科植物广泛分布于亚洲，非洲，澳大利亚和太平洋岛屿等热带和亚热带地区，是一种重要的中药材。马鞭草科豆腐柴属植物豆腐柴在中国已被广泛用于中医治疗痢疾和阑尾炎。我们目前已从该植物中分离鉴定了30种化合物，其中一个secoisolariciresinol型倍半木脂素化合物14为新化合物，除化合物9以外，其余均为首次从豆腐柴属植物中分离得到。对这些化合物进行药理活性筛选，并未出现总膏表现出的抗肿瘤的活性，我们推测仍有部分活性的物质有待分离。