Chu Ellie Shihng Meir, Wong Thomas Kwok Shing, Yow Christine Miu Ngan
Medical Laboratory Science, Department of Health Technology & Informatics, The Hong Kong Polytechnic University, HKSAR.
Photochem Photobiol Sci. 2008 Jan;7(1):76-83. doi: 10.1039/b703417b. Epub 2007 Nov 2.
Tumor invasion and immortality are the most unfavorable drawbacks after cancer treatment. In this study, we focus on determining the photodynamic modulation of the proteolytic enzymes, matrix metalloproteinases (MMP); and a core catalytic subunit of telomerase, the human telomerase reverse transcriptase (hTERT) in medulloblastoma (MED) cell line (TE-671). Hexvix (ALA-H) mediated photodynamic therapy (PDT) demonstrated greater efficacy than 5-aminolevulinic acid (5-ALA) in terms of drug uptake and anti-proliferative effect. Both MMP-2 and hTERT expression are down-regulated quantitatively using ELISA and reverse-transcriptase-PCR (RT-PCR) respectively at post-treatment for this cell line. The MMP-9 expression remains unchanged after treatment. Further, there is a statistically significant inhibition of cell migration at 24 h post-ALA-H-PDT at LD(50) (0.01 mM, 2 J cm(-2); p < 0.001) in MED TE-671 cells. Evidently, MMP-2 and hTERT mRNA expressions can be the targets for the photodynamic intervention on tumor cell migration and immortality. Hence, PDT may be an alternate cancer regime for medulloblastoma.
肿瘤侵袭和细胞永生是癌症治疗后最不利的缺点。在本研究中，我们专注于确定光动力对髓母细胞瘤（MED）细胞系（TE-671）中蛋白水解酶、基质金属蛋白酶（MMP）以及端粒酶的核心催化亚基——人类端粒酶逆转录酶（hTERT）的调节作用。在药物摄取和抗增殖作用方面，海姆泊芬（ALA-H）介导的光动力疗法（PDT）显示出比5-氨基酮戊酸（5-ALA）更高的疗效。对于该细胞系，在治疗后分别使用酶联免疫吸附测定（ELISA）和逆转录聚合酶链反应（RT-PCR）定量下调MMP-2和hTERT的表达。治疗后MMP-9的表达保持不变。此外，在MED TE-671细胞中，在ALA-H-PDT处理后24小时，在半数致死剂量（LD(50)）（0.01 mM，2 J cm(-2)；p < 0.001）时细胞迁移受到统计学上显著的抑制。显然，MMP-2和hTERT mRNA表达可以成为光动力干预肿瘤细胞迁移和永生的靶点。因此，PDT可能是髓母细胞瘤的一种替代癌症治疗方案。
