光动力疗法对小鼠恶性黑色素瘤的体内外效应

In vitro and in vivo effects of photodynamic therapy on murine malignant melanoma.

作者信息

Haddad R, Blumenfeld A, Siegal A, Kaplan O, Cohen M, Skornick Y, Kashtan H

机构信息

Department of Surgery A, Tel-Aviv Sourasky Medical Center, Israel.

出版信息

Ann Surg Oncol. 1998 Apr-May;5(3):241-7. doi: 10.1007/BF02303780.

DOI:10.1007/BF02303780

PMID:9607626

Abstract

BACKGROUND

The role of photodynamic therapy (PDT) in the treatment of malignant melanoma is not well defined, nor is it known whether the dark melanoma cells absorb the light used in PDT.

IN VITRO STUDIES

2 x 10(5) B16 murine melanoma cells were incubated with aluminum phthalocyanine (AlpcS4, 2.5 mg/kg) and were then subjected to photoradiation (50, 100 or 200 J/cm2). Viability was then assessed. In vivo studies:

HISTOLOGY

C57/B1 mice received 2 x 10(5) B16 cells subcutaneously and were randomized into study (PDT) and three control groups. AlpcS4 2.5 mg/kg was injected intraperitoneally and the mice were exposed to light (100 J/cm2). After 24 hours they were sacrificed and underwent autopsies. Survival: 40 mice were randomized into PDT (40 J/cm2) and control groups and were monitored for 50 days. Tumor growth: 40 mice were randomized into one control and three treatment groups (PDT on day 3, 6, or 12 after injection with B16 cells), and were monitored for 50 days. Temperature: Tumor temperatures before and at the end of PDT were recorded.

IN VITRO STUDIES

PDT caused a decrease in cell viability to 15.5 +/- 0.7%, 11.5 +/- 2.1%, and 1.5 +/- 0.7% (at 50, 100, and 200 J/cm2, respectively; P < .001). A significant reduction in thymidine incorporation was noted at all energy levels. In vivo studies:

HISTOLOGY

PDT caused massive tumor necrosis. Survival: PDT prolonged the survival of mice (41 +/- 13.4 days) compared to controls (15.8 +/- 3.8 days, P < .001). Tumor growth: 31 days after injection with B16 cells, the tumor size was 2.6 +/- 0.3 cm in the control group and 1.6 +/- 0.2, 0.9 +/- 0.3, and 1.0 +/- 0.4 cm in the PDT groups (days 3, 6 and 12, respectively; P < .01). Temperature: PDT increased skin temperature to 42.8 degrees C +/- 1.3 degrees C, 45.3 degrees C +/- 3.5 degrees C, and 51.7 degrees C +/- 2.7 degrees C at 40, 60, and 100 J/cm2, respectively (P < .01).

CONCLUSIONS

Photodynamic therapy was found to have significant effects in experimental melanoma in mice. The role of PDT in human melanoma remains to be studied.

摘要

背景

光动力疗法（PDT）在恶性黑色素瘤治疗中的作用尚未明确界定，也不清楚黑色素瘤暗细胞是否会吸收PDT中使用的光。

体外研究

将2×10⁵个B16小鼠黑色素瘤细胞与铝酞菁（AlpcS4，2.5毫克/千克）一起孵育，然后进行光辐射（50、100或200焦/平方厘米）。随后评估细胞活力。体内研究：

组织学

C57/B1小鼠皮下接种2×10⁵个B16细胞，并随机分为研究组（PDT）和三个对照组。腹腔注射2.5毫克/千克的AlpcS4，然后让小鼠接受光照（100焦/平方厘米）。24小时后将其处死并进行尸检。生存情况：40只小鼠随机分为PDT组（40焦/平方厘米）和对照组，并监测50天。肿瘤生长：40只小鼠随机分为一个对照组和三个治疗组（在注射B16细胞后第3、6或12天进行PDT），并监测50天。温度：记录PDT前及结束时的肿瘤温度。

体外研究

PDT使细胞活力分别降至15.5±0.7%、11.5±2.1%和1.5±0.7%（分别对应50、100和200焦/平方厘米；P<.001）。在所有能量水平下均观察到胸苷掺入量显著降低。体内研究：

组织学

PDT导致大量肿瘤坏死。生存情况：与对照组（15.8±3.8天，P<.001）相比，PDT延长了小鼠的生存期（41±13.4天）。肿瘤生长：注射B16细胞31天后，对照组肿瘤大小为2.6±0.3厘米，PDT组（分别在第3、6和12天）肿瘤大小为1.6±0.2厘米、0.9±0.3厘米和1.0±0.4厘米（P<.01）。温度：在40、60和100焦/平方厘米时，PDT分别使皮肤温度升高至42.8℃±1.3℃、45.3℃±3.5℃和51.7℃±2.7℃（P<.01）。