基于IL-6/STAT3 信号通路探寻蒙药玉簪花抗前列腺癌活性成分与分子机制

Prostate cancer (PCa) is the most common malignant tumor of the male reproductive system, its treatment with limited efficacy and side effects of larger, seeking new, safe and effective drugs are the important research direction for the treatment of PCa. The flowers of Hosta plantaginea (Lam.) Aschers (HPF) has a long history and commonly used Mongolian traditional medicine，it was used to treat prostatitis in the folk, modern pharmacological studies show that it also has an anti-tumor effect. In our pre-experiment, we had proved that the extracts from HPF significantly decreased the level of IL-6 in the tissue of prostatitis, inhibited the proliferation of prostate cancer cell and promoted its apoptosis. Its pharmacodynamic material base and molecular mechanism are not clear, which need to be further studied. On this basis, this project intends to study the separation, purification and structural identification of the effective parts of the anti-prostate cancer of the HPF, and to determine the effective components by SRB method. At the cellular level (prostate cancer cell DU145 and pc-3) and animal models (mouse xenograft model of prostate cancer), we study the molecular mechanism of active components in IL-6/STAT3 signaling pathway and related protein expression by western blot, qRT-PCR, gene overexpression, immunohistochemistry and other techniques and methods. We hope that the results of the study provides scientific basis for the comprehensive development and utilization of HPF and provides candidate compounds for the development of natural anti-prostate cancer drugs.

前列腺癌(PCa)是男性生殖系统最常见的恶性肿瘤，其治疗药物的疗效有限并且毒副作用较大，寻求新型、安全有效治疗PCa药物为临床应用研究的重要方向。玉簪花为蒙医临床常用药材，民间用于治疗前列腺炎，现代药理研究其具有抗肿瘤作用。前期研究证实，玉簪花正丁醇部位及水部位提取物有较强的抑制前列腺癌细胞生长并促细胞凋亡的作用，其药效物质基础与分子机制不清楚，有待深入研究。在此基础上，本项目拟对玉簪花抗前列腺癌有效部位进行分离、纯化及结构鉴定研究，并用SRB法筛选确定有效成分；在细胞水平（前列腺癌细胞DU145和PC-3）和动物模型（前列腺癌裸鼠移植瘤模型）层面上，应用westen blot、qRT-PCR、基因过表达，免疫组化等技术与方法研究有效成分作用于IL-6/STAT3信号通路及相关蛋白表达的分子机制。为玉簪花的综合开发利用提供科学依据，也为天然抗前列腺癌药物的研发提供候选化合物。

前列腺癌是男性生殖系统最常见的恶性肿瘤。玉簪花为蒙医临床常用药材，民间用于治疗前列腺炎，现代药理研究显示其具有抗肿瘤作用。本项目探讨了玉簪花抗前列腺癌的活性物质及其分子机制。我们通过体外实验发现玉簪花抗前列腺癌的活性部位为正丁醇部位，并对活性部位进行化学成分的分离与鉴定，从玉簪花活性部位鉴定出22个化合物，发现6个化合物具有抗前列腺癌活性。另外，利用体外细胞实验及体内皮下移植瘤模型研究玉簪花抗前列腺癌的作用机制，发现玉簪花活性部位可以促进前列腺癌细胞凋亡及周期阻滞，抑制前列腺癌细胞及皮下移植瘤中IL-6、p-STAT3、BCL2和Cyclin D1的表达；结果提示玉簪花可能通过抑制IL-6/STAT3信号通路、促进细胞凋亡及周期阻滞发挥抗前列腺癌作用，为进一步筛选玉簪花抗前列腺癌活性成分并深入研究其作用机制提供实验基础，为玉簪花抗前列腺癌的临床应用提供理论依据。