Zupkó I, Kamuhabwa A R, D'Hallewin M A, Baert L, De Witte P A
Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, B-3000 Leuven, Belgium.
Int J Oncol. 2001 May;18(5):1099-105.
In a recent clinical study, we showed that hypericin accumulates selectively in urothelial lesions of the bladder following intravesical administration of the compound in patients. This observation infers that hypericin, a potent photosensitizer, could be used as a selective photodynamic therapy (PDT) tool against superficial bladder cancer. In the present study we investigated the in vivo PDT activity of hypericin in transition cell carcinoma (TCC) tumors of the bladder. Both the distribution and tumor PDT response were carried out using subcutaneous heterotopic AY-27 TCC tumors in syngeneic rats. For both PDT and distribution studies, hypericin (1 or 5 mg/kg) was injected intravenously 0.5, 6 or 24 h before PDT or distribution evaluation. The data show that hypericin is a potent photosensitizer in the treatment of TCC tumors in vivo and that the interval between drug administration and photo-irradiation has a dramatic effect on the PDT outcome. Using a 0.5 h interval between drug administration and photo-irradiation the tumor regrowth study indicated that no tumor mass could me measured 9-10 days after PDT. On the contrary, lengthening the time interval between drug administration and photo-irradiation resulted in a gradual loss of PDT efficiency in these tumors. For instance, while the 6 h drug interval protocol produced a moderate PDT activity in which the tumor sizes decreased to about 50% of their original sizes 11-16 days after photo-irradiation, the 24 h interval protocol was even less effective. The distribution data indicate that the PDT efficiency of hypericin in TCC tumors corresponded to the plasma concentrations rather than to the over all concentrations in the tumor. It is therefore conceivable that the mechanism of PDT efficacy of hypericin in TCC tumors is through indirect (vascular effects) rather than through direct effects (cellular destruction) of hypericin in these tumors. In conclusion, our data indicate that hypericin is a potent photosensitizer against AY-27 TCC tumors and that the PDT efficacy of hypericin is largely determined by photosensitizer distribution in the tumor at the time of photo-irradiation.
在最近的一项临床研究中，我们发现，在向患者膀胱内灌注金丝桃素后，该化合物会选择性地在膀胱尿路上皮病变处蓄积。这一观察结果表明，强效光敏剂金丝桃素可作为针对浅表性膀胱癌的选择性光动力疗法（PDT）工具。在本研究中，我们调查了金丝桃素在膀胱移行细胞癌（TCC）肿瘤中的体内PDT活性。使用同基因大鼠皮下异位AY-27 TCC肿瘤进行分布和肿瘤PDT反应研究。对于PDT和分布研究，在PDT或分布评估前0.5、6或24小时静脉注射金丝桃素（1或5mg/kg）。数据表明，金丝桃素在体内治疗TCC肿瘤方面是一种强效光敏剂，给药与光照射之间的间隔对PDT结果有显著影响。在给药与光照射之间间隔0.5小时的肿瘤再生长研究表明，PDT后9-10天无法测量到肿瘤块。相反，延长给药与光照射之间的时间间隔会导致这些肿瘤中PDT效率逐渐丧失。例如，6小时给药间隔方案产生了中等程度的PDT活性，光照射后11-16天肿瘤大小降至其原始大小的约50%，而24小时间隔方案效果更差。分布数据表明，金丝桃素在TCC肿瘤中的PDT效率与血浆浓度而非肿瘤中的总体浓度相对应。因此，可以设想，金丝桃素在TCC肿瘤中的PDT疗效机制是通过间接（血管效应）而非金丝桃素在这些肿瘤中的直接效应（细胞破坏）。总之，我们的数据表明，金丝桃素是针对AY-27 TCC肿瘤的强效光敏剂，金丝桃素的PDT疗效在很大程度上取决于光照射时光敏剂在肿瘤中的分布。
