一种新型甾体皂苷抑制STAT3的分子机制及其在前列腺癌发生发展中的功能研究

STAT3异常激活与多种人类恶性肿瘤（如：前列腺癌）密切相关，发现和鉴定STAT3抑制物已经成为肿瘤治疗研究领域的一个热点。天然产物是STAT3抑制物的重要来源，但甾体皂甙与STAT3的关系目前基本没有报道。我们的前期研究已经分离纯化一种新型的甾体皂甙SH-8，并发现SH-8能够特异性抑制STAT3，限制肿瘤细胞的生长和迁移。为进一步探究SH-8的抗癌活性和分子机理，本研究拟以前列腺癌为模型，开展以下工作：1）揭示SH-8对STAT3的调控机制，鉴定其直接作用靶点；2) 利用细胞和小鼠肿瘤生长及转移模型，揭示SH-8和STAT3的相互作用及其在肿瘤生长和转移中的功能。本研究深入解析了新型甾体皂甙SH-8的功能和作用机制，为前列腺癌以及其它STAT3相关恶性肿瘤的预防、诊断和治疗提供新的潜在靶点，同时也将拓展STAT3抑制剂的来源和认识，促进相关领域的研究，具有一定的理论和现实意义。

The abnormal activation of STAT3 is implicated in many human malignant tumor (including prostate cancer), and identification of novel STAT3 inhibitors has become a popular research field on cancer therapy. Natural products are important sources of STAT3 inhibitors, and there are no report about the relationship of steroidal glycoside and STAT3. Our preliminary studies have been isolated and purified a novel steroidal glycoside named SH-8, and found that SH-8 can specifically inhibit phosphorylation of STAT3, limiting the growth and migration of tumor cells. By using prostate cancer as a model system, this proposal will investigate：1) to identify the direct target of SH-8 and uncover its molecular mechanism underlying STAT3 suppression; 2) to examine the effect of SH-8 in tumor growth and metastasis using tumor cells and mice model. This study will provide potential new targets for prevention, diagnosis and treatment of prostate cancer, as well as other STAT3-related malignant tumor, and will also expand the sources of STAT3 inhibitors, which promote the research in related fields.