Chekulayeva Lyudmila V, Shevchuk Igor N, Chekulayev Vladimir A
Department of Chemistry of Tallinn University of Technology, Tallinn 12618 Estonia.
Exp Oncol. 2004 Jun;26(2):125-39.
To elucidate the mechanism of the potentiating influence of heating associated with photoirradiation on the antitumor efficiency of photodynamic therapy (PDT) with hematoporphyrin derivative (HPD).
The study was carried out on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in a serum-free medium and then irradiated with red light (lambda max=630 nm) at various temperatures. Cytotoxicity was estimated by the trypan blue exclusion assay.
Our data support the view that in PDT the hyperthermia (around 44 degrees C) produced by irradiation can enhance synergistically the HPD-photoinduced tumor eradication; it was found that raising the irradiation temperature from 30 to 44 degrees C caused a substantial (approximately 1.5 fold) increase in the rate of HPD-photosensitized inactivation of EAC cells, while hyperthermia (44 degrees C) itself showed little toxic effects towards the cells.
Studies indicated that the potentiating effect of heating on the antitumor efficiency of HPD-PDT could be largely explained by the stimulation of reactive oxygen species formation such as H2O2, superoxide and hydroxyl radicals. It was also found that photosensitization of EAC cells by HPD caused a strong fall in the activity of catalase (CAT) and glutathione (GSH) peroxidase, and that heating sensitized the H2O2-detoxifying enzymes to HPD-photoinduced inactivation. Under HPD-PDT, these events could result in loss of protection against accumulating H2O2; we revealed that cell-bound CAT and the GSH redox cycle play an important role in the protection of EAC cells against HPD-PDT. Moreover, our findings suggest that during PDT with HPD, an increase in the temperature of tumors could enhance the efficiency of this therapy via the stimulation of a chlorin-type photoproduct formation.
阐明光照射相关加热对血卟啉衍生物（HPD）光动力疗法（PDT）抗肿瘤效率的增强作用机制。
对艾氏腹水癌（EAC）细胞进行研究，细胞在无血清培养基中加载HPD，然后在不同温度下用红光（λmax = 630 nm）照射。通过台盼蓝排斥试验评估细胞毒性。
我们的数据支持这样的观点，即在PDT中，照射产生的热疗（约44℃）可协同增强HPD光诱导的肿瘤根除；发现将照射温度从30℃提高到44℃会使EAC细胞的HPD光致敏失活率大幅（约1.5倍）增加，而热疗（44℃）本身对细胞显示出很小的毒性作用。
研究表明，加热对HPD-PDT抗肿瘤效率的增强作用很大程度上可通过刺激活性氧的形成来解释，如过氧化氢、超氧化物和羟基自由基。还发现HPD对EAC细胞的光致敏导致过氧化氢酶（CAT）和谷胱甘肽（GSH）过氧化物酶的活性大幅下降，并且加热使H2O2解毒酶对HPD光诱导的失活敏感。在HPD-PDT下，这些事件可能导致对积累的H2O2失去保护；我们揭示细胞结合的CAT和GSH氧化还原循环在保护EAC细胞免受HPD-PDT方面起重要作用。此外，我们的研究结果表明，在使用HPD的PDT过程中，肿瘤温度的升高可通过刺激氯型光产物的形成来提高这种治疗方法的效率。
