光动力学治疗诱导舌癌裸鼠肿瘤模型中活性氧离子发生特性及其与抗肿瘤效应的相关性

Properties of reactive oxygen species germination induced by photodynamic therapy and its association with anti-tumor effect in nude mouse tongue cancer model

目的利用新型的近红外多光谱检测系统(NIR-PMT),在不同光动力学治疗(PDT)条件下对单态氧离子(1O2)发生情况进行实时监测,并探讨其发生特性与PDT抗肿瘤效果之间的相关性。方法皮下注射人舌癌细胞株(HSC-3)单细胞悬液建立HSC-3细胞株裸鼠皮下移植瘤模型,实验动物随机分为PDT组(n=15)及对照组(n=10)。PDT组以盐酸氨基乙酰丙酸(5-ALA)为光敏剂加激光光照射进行PDT。对照组不采用5-ALA和/或光照射。检测肿瘤组织中原卟啉Ⅸ(PpⅨ)荧光水平及舌癌组织中PDT诱导活性氧离子发生情况,观察PDT治疗后舌癌皮下移植瘤的组织学变化及对皮下移植瘤的生长抑制作用,对5-ALA诱导的PDT在舌癌模型中的远期疗效进行评估。结果实验中清晰的观察到了1O2发生情况。PDT过程中1O2表现出明显的功率及能量依赖性。高照射功率诱导高水平的1O2发生,从而产生较强的抗肿瘤效果。舌癌裸鼠皮下移植瘤在PDT治疗后90 d内,与对照组相比肿瘤生长受到明显抑制,但在2例体积较大的肿瘤中观察到复发迹象。结论1O2发生与PDT的抗肿瘤效果有着密切关系;尽管以5-ALA为光敏剂诱导的PDT在舌癌裸鼠模型中显示了强大的抗肿瘤特性,但该方法更适于口腔部小肿瘤的治疗。

Objective To real-time monitor the situation of singlet oxygen （1O2 ） germination under the condition of different photodynamic therapy （ PDT ） with new-type near infrared photomuhiplier tube （ NIR-PMT ） and explore its association with anti-tumor effect of PDT. Methods The tongue cancer subcutaneous transplanted tumor model of nude nmuse was established by subcutaneous injection of single cell suspension of human tongue cancer cell line HSC-3. The experimental animals were randomly divided into PDT group （n = 15 ） and control group （n = 10）. In PDT group, PDT was performed by 5-aminolevulinie acid hydrochloride （ 5-ALA ） as photosensitizer plus laser radiation. In control group, no treatment of 5-ALA and/or light radiation was given. Protoporphyrin IX （ Pp IX ） fluorescence level in tumor tissues and situation of PDT-induced reactive oxygen species germination in tongue cancer tissues were detected. Histological changes of tongue cancer subcutaneous transplanted tumor and its growth inhibitory effect after PDT were observed, and the long-term efficacy of 5-ALA-induced PDT in tongue cancer model was assessed. Results The occurrence of 1O2 was clearly observed in the experiment. The generation of 1O2 in the process of PDT showed a significant power- and energy-dependence. High output radiation can induce generation of high level 1O2 thus result in strong antitumor effect. Compared with control group, tumor growth in tongue cancer subcutaneous transplanted tumor of nude mice was significantly inhibited, however, there was a sign of recurrence in 2 mice with larger tumors. Conclusions The germination of 1O2 is closely related to the anti-tumor effect of PDT. Though PDT using 5-ALA as photosensitizer shows strong anti-tumor properties in the nude mice model of tongue cancer,it is more suitable for oral cavity small tumors.