Combination of photodynamic therapy and temozolomide on glioma in a rat C6 glioma model

被引：27

作者：

Zhang, Xiaoming ^{[1
]}

Guo, Mian ^{[1
]}

Shen, Lei ^{[2
]}

Hu, Shaoshan ^{[1
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 2, Dept Neurosurg, Harbin 150086, Peoples R China

[2] Qiqihar Med Univ, Dept Cardiol, Qiqihar 161006, Peoples R China

来源：

PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY | 2014年 / 11卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Blood-tumor barrier; Glioma; P-glycoprotein; Photodynamic therapy; Temozolomide; HEMATOPORPHYRIN MONOMETHYL ETHER; P-GLYCOPROTEIN; ANTITUMOR IMIDAZOTETRAZINES; ADJUVANT TEMOZOLOMIDE; MULTIDRUG-RESISTANCE; ACQUIRED-RESISTANCE; MALIGNANT GLIOMAS; CELL-LINES; HELA-CELLS; APOPTOSIS;

D O I：

10.1016/j.pdpdt.2014.10.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: For glioma, temozolomide (TMZ) is a commonly used chemotherapy drug and photodynamic therapy (PDT) is an important adjuvant therapy. The aim of this study was to evaluate the effect of their combination for the treatment of glioma. Methods: A rat C6 glioma model using male Wistar rats (n=180) weighing 280-300 g was established. Glioma-bearing rats (n=100) were treated with mock, hematoporphyrin monomethyl ether (HMME), laser or PDT. The expression of P-glycoprotein (P-gp) in endothelial cells of the blood tumor-barrier and in glioma tissues was detected using immunohistochemistry and western blot, respectively. Glioma-bearing rats (n = 40) were treated with normal saline, TMZ (60 mg/m(2) for five consecutive days), PDT (630 nm for 10 min) or a combination of TMZ and PDT. TMZ concentration in glioma tissues was detected using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) and cell death was observed using transmission microscopy. Concurrently, another batch of 40 glioma-bearing rats was subjected to the same treatment, and the survival of these rats was estimated using Kaplan-Meier analysis. Results: PDT significantly decreased the expression of P-gp in endothelial cells comprising the blood tumor-barrier and in glioma tissues. The combination of TMZ with PDT significantly increased TMZ concentration in glioma tissues, enhanced glioma cell apoptosis and prolonged the median survival of glioma-bearing rats. Conclusion: The combination of PDT with TMZ shows synergistic effect in rat C6 glioma model, indicating its potential clinical use in glioma treatment. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：603 / 612

页数：10

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