Chakrabarti P, Orihuela E, Egger N, Neal D E, Gangula R, Adesokun A, Motamedi M
Department of Surgery, University of Texas Medical Branch, Galveston 77555, USA.
Prostate. 1998 Sep 1;36(4):211-8. doi: 10.1002/(sici)1097-0045(19980901)36:4<211::aid-pros1>3.0.co;2-i.
Delta-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is currently being investigated for the treatment of prostate diseases. In this study, we evaluate 1) the in vitro production of protoporphyrin IX (PPIX) (the active photosensitizing agent of ALA-mediated PDT) by two different prostate cancer cell lines (LNCaP and PC-3) and a benign, modified, prostatic cell line (TP-2), and 2) the extent of PDT-induced cell injury, as determined by electron microscopy (EM) and cell survival.
The cell lines were assigned into four treatment groups: group 1, control, no ALA and no light irradiation; group 2, dark control, ALA only; group 3, light control, radiation only; and group 4, PDT, ALA followed by irradiation (630 nm, 3 joules/cm2). The experiments were performed in triplicate. ALA concentration was 50 microg/ml of media in all instances.
Following incubation with ALA, PPIX production was significantly increased in the three cell lines studied, and more notably in the PC-3 cell line. Compared to controls, EM and cell survival studies demonstrated significant mitochondrial damage and decreased survival, respectively, in the cells treated with PDT. This was also more evident in the PC-3 cell line.
Our results demonstrate that prostate cells differ in their response to ALA-mediated PDT. This response appears to depend on the intracellular production of PPIX and the cell type, i.e., on the functional and structural characteristics of the cell mitochondria. In addition, our results suggest that PDT might be effective at killing prostate cancer cells.
δ-氨基乙酰丙酸(ALA)介导的光动力疗法(PDT)目前正在用于前列腺疾病治疗的研究。在本研究中,我们评估了:1)两种不同的前列腺癌细胞系(LNCaP和PC-3)以及一种良性的、改良的前列腺细胞系(TP-2)体外原卟啉IX(PPIX,ALA介导的PDT的活性光敏剂)的生成情况;2)通过电子显微镜(EM)和细胞存活情况测定的PDT诱导的细胞损伤程度。
将细胞系分为四个处理组:第1组为对照组,不使用ALA且不进行光照;第2组为暗对照组,仅使用ALA;第3组为光对照组,仅进行照射;第4组为PDT组,先使用ALA然后进行照射(630nm,3焦耳/平方厘米)。实验重复进行三次。所有情况下ALA浓度均为50微克/毫升培养基。
与ALA孵育后,在所研究的三种细胞系中PPIX生成均显著增加,在PC-3细胞系中更明显。与对照组相比,EM和细胞存活研究分别显示,接受PDT处理的细胞中线粒体有明显损伤且存活率降低。这在PC-3细胞系中也更明显。
我们的结果表明前列腺细胞对ALA介导的PDT的反应存在差异。这种反应似乎取决于PPIX的细胞内生成以及细胞类型,即取决于细胞线粒体的功能和结构特征。此外,我们的结果表明PDT可能对杀死前列腺癌细胞有效。