Date Masataka, Sakata Isao, Fukuchi Kazuhide, Ohura Kiyoshi, Azuma Yasutaka, Shinohara Mitsuko, Matsuzaki Koichi, Namiki Yoshihisa, Takahashi Hiroshi
Department of Pharmacology, Osaka Dental University, Hirakata 573-1121, Japan.
Lasers Surg Med. 2003;33(1):57-63. doi: 10.1002/lsm.10188.
Photodynamic therapy (PDT) is a novel and promising cancer treatment that employs a combination of photosensitizer and visible light. We examined the effect of PDT using a new photosensitizer, PAD-S31, and the 670-nm diode laser in human oral squamous cell carcinomas (SCC).
STUDY DESIGN/MATERIALS AND METHODS: SAS and HSC-4 cell lines were used in all the experiments. Cell viability was determined by a modified MTT assay. Two methods were used for the determination of apoptosis in human oral SCC cells: TUNEL assay and detection of fragmented mono- and oligo-nucleosomes by ELISA. Xenografts of human oral SCC cells were generated in KSN S1c nude mice.
In vitro PDT using PAD-S31 and the 670-nm diode laser showed cytotoxicity that was a function of laser energy, drug concentration, and time to the SAS and HSC-4 cell lines. On the other hand, PAD-S31 without irradiation had no effect on cell viability. The combinated use of PAD-S31 and the laser irradiation showed excellent anti-tumor activity against tumor xenografts without severe side effects. PDT-mediated cell death occurred predominantly by apoptosis in vitro and in vivo.
The present study demonstrates that PAD-S31 may serve as a potent photosensitizer for PDT. Furthermore, it is expected that this therapy will be clinically useful for the treatment of patients with oral carcinoma.
光动力疗法(PDT)是一种新型且有前景的癌症治疗方法,它采用光敏剂和可见光相结合的方式。我们研究了使用新型光敏剂PAD - S31和670纳米二极管激光进行光动力疗法对人口腔鳞状细胞癌(SCC)的影响。
研究设计/材料与方法:所有实验均使用SAS和HSC - 4细胞系。通过改良的MTT法测定细胞活力。采用两种方法测定人口腔鳞状细胞癌细胞的凋亡情况:TUNEL法和通过ELISA检测单核小体和寡核小体片段。在KSN S1c裸鼠体内建立人口腔鳞状细胞癌细胞异种移植模型。
使用PAD - S31和670纳米二极管激光进行的体外光动力疗法对SAS和HSC - 4细胞系显示出细胞毒性,这种毒性是激光能量、药物浓度和时间的函数。另一方面,未照射的PAD - S31对细胞活力没有影响。PAD - S31与激光照射联合使用对肿瘤异种移植模型显示出优异的抗肿瘤活性,且无严重副作用。光动力疗法介导的细胞死亡在体外和体内主要通过凋亡发生。
本研究表明PAD - S31可能作为光动力疗法的一种有效光敏剂。此外,预计这种疗法在临床上对口腔癌患者的治疗将具有实用性。