PDF(Pubmed)
Abstract：
Oral squamous-cell and pancreatic carcinomas are aggressive cancers with a poor outcome. Photodynamic therapy (PDT) consists of the use of photosensitizer-induced cell and tissue damage that is activated by exposure to visible light. PDT selectively acts on cancer cells, which have an accumulation of photosensitizer superior to that of the normal surrounding tissues. 5-aminolevulinic acid (5-ALA) induces the production of protoporphyrin IX (PpIX), an endogenous photosensitizer activated in PDT. This study aimed to test the effect of a new gel containing 5% v/v 5-ALA (ALAD-PDT) on human oral CAL-27 and pancreatic CAPAN-2 cancer cell lines. The cell lines were incubated in low concentrations of ALAD-PDT (0.05%, 0.10%, 0.20%, 0.40%, 0.75%, 1.0%) for 4 h or 8 h, and then irradiated for 7 min with 630 nm RED light. The cytotoxic effects of ALAD-PDT were measured using the MTS assay. Apoptosis, cell cycle, and ROS assays were performed using flow cytometry. PpIX accumulation was measured using a spectrofluorometer after 10 min and 24 and 48 h of treatment. The viability was extremely reduced at all concentrations, at 4 h for CAPAN-2 and at 8 h for CAL-27. ALAD-PDT induced marked apoptosis rates in both oral and pancreatic cancer cells. Elevated ROS production and appreciable levels of PpIX were detected in both cell lines. The use of ALA-PDT as a topical or intralesional therapy would permit the use of very low doses to achieve effective results and minimize side effects. ALAD-PDT has the potential to play a significant role in complex oral and pancreatic anticancer therapies.
摘要：
口腔鳞状细胞癌和胰腺癌是预后较差的侵袭性癌症。光动力疗法(PDT)包括使用通过暴露于可见光而激活的光敏剂诱导的细胞和组织损伤。PDT选择性地作用于癌细胞，其光敏剂的积累优于正常周围组织。5-氨基乙酰丙酸（5-ALA）诱导原卟啉IX（PpIX）的产生，在PDT中激活的内源性光敏剂。这项研究旨在测试含有5％v/v5-ALA（ALAD-PDT）的新型凝胶对人口腔CAL-27和胰腺CAPAN-2癌细胞系的影响。将细胞系在低浓度的ALAD-PDT（0.05％，0.10%,0.20%，0.40%，0.75%,1.0%)4小时或8小时，然后用630nm的红光照射7分钟。使用MTS测定法测量ALAD-PDT的细胞毒性作用。细胞凋亡,细胞周期,和ROS测定使用流式细胞术进行。在处理10分钟以及24和48小时后，使用分光荧光计测量PpIX的积累。在所有浓度下，活力都大大降低，CAPAN-2在4小时，CAL-27在8小时。ALAD-PDT在口腔和胰腺癌细胞中诱导显著的凋亡率。在两种细胞系中均检测到升高的ROS产生和可观的PpIX水平。使用ALA-PDT作为局部或病灶内治疗将允许使用非常低的剂量以获得有效的结果并使副作用最小化。ALAD-PDT具有在复杂的口服和胰腺抗癌疗法中发挥重要作用的潜力。
