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[光动力疗法对裸鼠人食管癌异种移植物的作用机制]

[Mechanism of photodynamic therapy against human esophageal carcinoma xenografts in nude mice].

作者信息

Chen Xiao-Hua, Luo Rong-Cheng, Li Li-Bo, Ding Xue-Mei, Lv Cheng-Wei, Zhou Xiao-Ping, Yan Xiao

机构信息

Center of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. cxh0663 @yahoo.com.cn

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2009 Nov;29(11):2222-4.

PMID:19923072
Abstract

OBJECTIVE

To investigate the mechanism of photodynamic therapy (PDT) in nude mice bearing human esophageal cancer cell line Eca-109 xenografts.

METHODS

A nude mouse model bearing human esophageal carcinoma was established by subcutaneous transplantation of Eca-109 cells. The mice were then randomized into 4 groups, namely hematoporphyrin derivative (HpD)-PDT group (given HpD and laser irradiation), exclusive laser irradiation group, exclusive HpD group and blank control group. In HpD-PDT group, the mice were exposed to irradiation at the light energy density of 120 Jsol;cm(2) delivered via a DIOMED 630 PDT system 24 h after intraperitoneal HpD injection, and the mice in exclusive laser irradiation group received only laser irradiation. Three days later, all the nude mice were sacrificed for determination of malondialdehyde (MDA) production, immunohistochemistry for caspase-3 protein and HE staining of the tumor tissue.

RESULTS

The MDA level was significantly higher in HpD-PDT group than in the other 3 groups (P<0.01), and comparable between the latter 3 groups. Expression of caspase-3 protein was similar between HpD-PDT group and the blank control group (P>0.05). Under light microscope, HE staining visualized massive tissue necrosis in HpD-PDT group with homogeneous red staining.

CONCLUSION

In human esophageal carcinoma xenografts in nude mice, HpD-PDT generates singlet oxygen to result in direct tumor cell damage and cause MDA production. Caspase-3 may not be activated in the apoptotic pathway, suggesting that this pathway may not be caspase-3-dependent.

摘要

目的

探讨光动力疗法(PDT)对荷人食管癌Eca-109细胞系裸鼠移植瘤的作用机制。

方法

将Eca-109细胞皮下接种于裸鼠,建立荷人食管癌裸鼠模型。然后将小鼠随机分为4组,即血卟啉衍生物(HpD)-PDT组(给予HpD并进行激光照射)、单纯激光照射组、单纯HpD组和空白对照组。在HpD-PDT组中,腹腔注射HpD 24 h后,通过DIOMED 630 PDT系统以120 J/cm²的光能密度进行照射,单纯激光照射组小鼠仅接受激光照射。3天后,处死所有裸鼠,测定丙二醛(MDA)含量,进行caspase-3蛋白免疫组化检测及肿瘤组织苏木精-伊红(HE)染色。

结果

HpD-PDT组MDA水平显著高于其他3组(P<0.01),后3组之间差异无统计学意义。HpD-PDT组与空白对照组caspase-3蛋白表达相似(P>0.05)。光镜下,HE染色显示HpD-PDT组有大量组织坏死,呈均匀红色染色。

结论

在荷人食管癌裸鼠移植瘤中,HpD-PDT产生单线态氧,直接损伤肿瘤细胞并导致MDA生成。凋亡途径中caspase-3可能未被激活,提示该途径可能不依赖caspase-3。

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