目前对于雄激素非依赖性前列腺癌（AIPC）仍然缺乏有效的治疗药物，由于其发病机制复杂，寻找能够作用于多靶点的抗AIPC药物具有重要意义。本课题组在对酸浆属植物活性成分的研究中，首次发现其中特有的酸浆苦素类甾体内酯具有诱导激素非依赖性前列腺癌细胞CWR22Rvl和C42B发生凋亡和抑制细胞中雄激素受体（AR）表达和功能的双重作用，且对人正常细胞的毒性较小，提示该类化合物可能通过多个靶点作用于AIPC细胞而发挥抗癌作用。本项目拟在上述研究工作的基础上，采用体外活性测试结合TLC和NMR快速识别检测方法，继续对酸浆属药用植物中含有的酸浆苦素类成分进行追踪分离，评价其对AIPC细胞的增殖抑制活性，并深入研究其抗癌作用机制及作用靶点，探讨该类型化合物的抗癌构效关系。本项目的实施完成将为新的抗雄激素非依赖性前列腺癌药物的发现奠定实验研究基础，并为阐明酸浆属药用植物发挥传统功效的物质基础提供科学依据。

Currently, there is no effective therapeutic method to treat androgen-independent prostate cancer (AIPC) for the extremely complex mechanism of AIPC pathogenesis. It is very significant for us to find out some new multiple targeted anticancer drugs for the treatment of AIPC. In our previous study, we demonstrated that physalin-type steroid lactones （physalin A and pysalin B）not only induced apoptosis of two androgen-independent cell lines, CWR22Rv1 and C42B, but also decreased androgen receptor (AR) expression, suggesting that they exert anticancer activity via multiple targets. And both compounds showed lower toxicity on human normal cell than the positive control. Therefore, further investigation will be done in this project based on our previous work, including: a) isolation and identification of more physalin-type steroid lactones from the medicinal plants of Physalis genus under the guidance of bioactivity assay in vitro, in combination with TLC and NMR analyses, b) determination of the growth inhibitory activity of the isolated physalin-type steroid lactones against CWR22Rv1 and C42B cell lines, c) further elucidation of the anticancer mechanism and targets of the active compounds by using Flow Cytometry, Western Blot and luciferase analysis, etc, d) clarification of the structure-activity relationships of physalin-type steroid lactones by the method of computer-aided drug design software. The purpose of this project is to provide scientific supports for the discovery of novel therapeutic agents for AIPC and for the interpretation of traditional use of Physalis genus.