补肾祛瘀法调控PI3K/AKT通路延缓前列腺癌向雄激素非依赖转化的研究

项目名称： 补肾祛瘀法调控PI3K/AKT通路延缓前列腺癌向雄激素非依赖转化的研究

项目编号： No.30873268

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 王伊光

作者单位： 北京中医药大学

项目金额： 31万元

中文摘要： 前列腺癌由雄激素依赖性（AIPC）向非依赖性（ADPC）转化是导致去势治疗失败的主要原因。本项目将延缓前列腺癌向ADPC转变作为中医药介入前列腺癌治疗的切入点，研究补肾祛瘀法对疾病转化中关键的信号通路PI3K/AKT/PTEN途径的调控作用。结果表明，具有补肾祛瘀作用的前癌消对未经去势治疗的AIPC有一定的促增长作用，而对经去势治疗的前列腺癌有增强去势治疗效果的作用及延缓去势后向ADPC转化的作用。体外细胞实验也表明，前癌消对AIPC细胞可能有一定的促进生长作用，而与雄激素剥夺治疗联合使用，可加强雄激素剥夺治疗对前列腺癌细胞生长的抑制作用。前癌消的作用与PI3K-AKT-PTEN信号途径有关，可能通过促进PTEN的磷酸化而抑制AKT的活化，从而抑制肿瘤细胞的增殖、促进肿瘤细胞的凋亡，延缓前列腺癌向ADPC转化。该研究为临床应用补肾祛瘀法治疗前列腺癌的时机提供了实验依据，在AIPC期应慎用补肾类药物，以防类雄激素样作用促进前列腺癌细胞的生长；在去雄治疗后应用补肾祛瘀法，可增强去势治疗的效果及延缓前列腺癌向ADPC转化。该研究也为阐明补肾祛瘀法延缓ADPC转化的分子机制提供了实验依据。

中文关键词： 前列腺癌；雄激素依赖性前列腺癌；雄激素非依赖性前列腺癌；补肾祛瘀；PI3K-AKT途径

英文摘要： Transformation of prostate cancer from androgen dependent to independent is the main cause responsible for failure of castration in treating it.This project will deal with how Traditional Chinese Medicine plays a crucial role in deferring prostate cancer from ADPC to AIPC and will study the regulatory effect of the TCM therapy of "tonifying kidney and removing stasis" on PI3K/AKT pathway, a pivotal signaling pathway in the transformation of the disease.Results demonstrate that "Qianaixiao Formula" ,one of "tonifying kidney and removing stasis"effect,aggravates the AIPC featuring no castration,while enhancing the effect of castration on AIPC.At the same time,the formula defers the transformation to AIPC.The experiment in vivo also shows that "Qianaixiao Formula" ,though facilitating the growth of AIPC cells possibly,enhances the inhibiting effect of castration when applied together with castration."Qianaixiao Formula"regulates the PI3K/PTEN/AKT pathway by promoting phosphorylation of PTEN,which gives rise to the activation of AKT later.All these contribute to the inhibition of tumor proliferation,acceleration of tumor apoptosis,thus deferring the transformation to AIPC.The research is a solid evidence for reasonable practices of "tonifying kidney and removing stasis"in treating prostate cancer in clinical medicine.Herbs tonifying kidney should be cautioned in ADPC lest the growth of tumor cells due to the so-called resembling androgens effects.Only after the castration can the treatment of "tonifying kidney and removing stasis" be used,which can enhance the existing effect and defer the transformation to AIPC as well.The research also provides evidence on how AIPC can be deferred from a molecular basis through the method of "tonifying kidney and removing stasis"

英文关键词： prostate cancer;ADPC;AIPC;tonifying kidney and removing stasis;PI3K-ATK pathway