PSCA介导左旋棉酚纳米粒子联合放射治疗诱导前列腺癌细胞凋亡与自噬的体内外生物学研究

前列腺干细胞抗原（PSCA）作为重要的特异性靶分子正成为单抗结合放化疗治疗前列腺癌的迫切需求，左旋棉酚作为Bcl-2最为有效的小分子抑制剂，不仅可以诱导前列腺癌细胞凋亡和自噬，还可增强放化疗敏感性，然而关于其联合放射能否诱导肿瘤细胞发生自噬及抑制自噬联合放射能否增强左旋棉酚在体抑制肿瘤增殖的研究仍是亟待探索的热点问题，此外左旋棉酚给药途径单一极大限制了其临床的进一步应用，鉴于此，本项目拟通过制备一种集靶向、示踪和治疗为一体的左旋棉酚纳米粒子，采用形态学与分子生物学相结合的方法，探讨其联合放射诱导前列腺癌细胞发生自噬与凋亡的量效关系及其潜在分子机制，同时联合自噬抑制剂，对其放射治疗前列腺癌的疗效进行在体、连续、无创的实时监测。本项目的顺利开展，不仅为前列腺癌的临床综合治疗提供新方法，开辟新途径，同时又为Bcl-2小分子抑制剂类型的抗肿瘤药物联合放射治疗前列腺癌提供重要实验数据和理论参考。

Prostate stem cell antigen (PSCA) as an important specific target is becoming the urgent for treatment of prostate cancer combined with radiotherapy and chemotherapy. Gossypol, as an effective small molecule inhibitors targetting to Bcl-2 protein, can not only induce apoptosis and autophagy in prostate cancer cells but also enhance the radiosensitization. However, there are not many report with regard to the relationship between radiation-induced apoptosis and autophagy as well as the radiotherapy effect combined with autophagy inhibitor. In addition, the single administration of gossypol also greatly limit its further clinical application. In view of these, we propose to prepare a novel multifunctional gossypol nanoparticles and study the dose-effect relationship and its potential molecular mechanism combined with radiotherapy in prostate cancer cells between the autophagy and apoptosis by using the method of morphological and molecular biology, Meanwhile, the therapeutic effect evaluation joint with autophagy inhibitor is conducted by optical molecular imaging technology.This project will not only provide a new method for the treatment of prostate cancer as well as provided important experimental data for small molecule Bcl-2 inhibitor combined with radiotherapy.