Sharma Prachi, Farrell Thomas, Patterson Michael S, Singh Gurmit, Wright James R, Sur Ranjan, Rainbow Andrew J
Department of Biology, McMaster University, Hamilton, ON, Canada.
Photochem Photobiol. 2009 Jan-Feb;85(1):99-106. doi: 10.1111/j.1751-1097.2008.00401.x. Epub 2008 Jul 17.
It has been suggested that combination high dose rate (HDR) intraluminal brachytherapy and photodynamic therapy (PDT) in nonsmall cell lung cancer (NSCLC) may improve efficacy of treatment, reduce toxicity and enhance quality of life for patients. To provide a cellular basis for this we examined the in vitro sensitivity of MRC5 normal lung fibroblasts and four NSCLC cell lines following HDR radiation, PDT and combined HDR radiation and PDT. HDR radiation was cobalt-60 gamma rays (1.5-1.9 Gy min(-1)). For PDT treatment, cells were exposed to 2.5 microg mL(-1) Photofrin for 18-24 h followed by light exposure (20 mW cm(-2)). For combined treatment cells were exposed to Photofrin and then either exposed to light and 15-30 min later exposed to HDR radiation or exposed to HDR radiation and 15-30 min later exposed to light. D(37) values calculated from clonogenic survival curves indicated a six-fold difference in HDR radiation sensitivity and an eight-fold difference in PDT sensitivity. The effect of combined treatment was not significantly different from an additive effect of the individual treatment modalities for the NSCLC cells, but was significantly less than additive for the MRC5 cells. These results suggest an equivalent tumor cell kill may be possible at reduced systemic effects to patients.
有人提出,在非小细胞肺癌(NSCLC)中,高剂量率(HDR)腔内近距离放射疗法与光动力疗法(PDT)联合使用可能会提高治疗效果,降低毒性并提高患者的生活质量。为了为此提供细胞基础,我们检测了MRC5正常肺成纤维细胞和四种NSCLC细胞系在HDR放射、PDT以及HDR放射与PDT联合治疗后的体外敏感性。HDR放射采用钴-60γ射线(1.5 - 1.9 Gy min⁻¹)。对于PDT治疗,细胞先暴露于2.5 μg mL⁻¹的卟吩姆钠18 - 24小时,然后进行光照(20 mW cm⁻²)。对于联合治疗,细胞先暴露于卟吩姆钠,然后要么先进行光照,15 - 30分钟后再进行HDR放射,要么先进行HDR放射,15 - 30分钟后再进行光照。从克隆形成存活曲线计算出的D(37)值表明,HDR放射敏感性有6倍差异,PDT敏感性有8倍差异。联合治疗对NSCLC细胞的效果与单独治疗方式的相加效应无显著差异,但对MRC5细胞的效果明显小于相加效应。这些结果表明,在降低对患者的全身影响的情况下,可能实现等效的肿瘤细胞杀伤。