前列腺癌是常见的恶性肿瘤,目前已将前列腺癌加入到适合接受光动力治疗的肿瘤类型中。PDT是将药物与光结合起来治疗肿瘤的一种新方法，MPPa是叶绿素的衍生物。其易于在前列腺癌PC-3M中富集并可以通过光动力作用杀伤癌细胞，对正常细胞基本无杀伤作用；它的细胞毒作用,表现为在低剂量时即可通过线粒体途径诱导细胞凋亡；此外我们还研究了缺氧的影响，以上研究发表于BBRC和LPL等期刊。本项目在申请人前期研究工作（疗效、机制、影响因素）基础上将MPPa-PDT与HSV1-TK/GCV治疗联合以提高治疗效果，完善整个MPPa-PDT的研究。方法是在细胞水平和荷瘤裸鼠水平转染HSV1-TK入PC-3M，随后加入GCV，该治疗同时联合MPPa-PDT。在细胞水平,镜下观察细胞形态改变,并通过MTT实验和流式细胞仪来明确该联合治疗对癌细胞的杀伤力；在动物水平，比较治疗组和对照组肿瘤的质量体积，并行光镜和电镜检测。

Prostate carcinoma is the common malignant tumor, the incidence increases with age. Photodynamic therapy is a new technique applied in tumors, which involves the administration of a tumor localizing photosensitizer and it is followed by the activation of a specific wavelength. I found that MPPa, a derivative of chlorophyll, is a novel potent photosensitizer. Our previous work in vitro and in vivo indicated that MPPa is a comparatively ideal photosensitizer on prostate carcinoma PC-3M and it is worth further investigation. Ganciclovir (GCV) is a guanosine analog used as a prodrug to obtain a suicide effect in cells transfected with HSV1-TK which can be activated by Grp78 promoter. HSV1-TK phosphorylates GCV to GCV-monophosphate which is further converted to GCV-diphosphate and GCV-triphosphate. GCV-triphosphate causes apoptosis. We are trying to find out whether it is a good way to improve the treatment effect by combination of MPPa-PDT and HSV1-TK/GCV therapy in vitro and in vivo.