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二甲双胍和阿霉素对可移植肿瘤模型的影响。

Effect of metformin and adriamycin on transplantable tumor model.

作者信息

Kabel Ahmed M, Omar Mohamed S, Balaha Mohamed F, Borg Hany M

机构信息

Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia; Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Division of Biochemistry, Pharmacology and Toxicology Department, College of Pharmacy, Taif University, Taif, Saudi Arabia; Chemistry Department, Faculty of Science, Benha University, Benha, Egypt.

出版信息

Tissue Cell. 2015 Oct;47(5):498-505. doi: 10.1016/j.tice.2015.07.003. Epub 2015 Jul 26.

Abstract

Adriamycin is a cytotoxic anthracycline antibiotic used in treatment of many types of cancer. Metformin is antidiabetic drug and is under investigation for treatment of cancer. The aim of this work was to study the effect of each of adriamycin and metformin alone and in combination on solid Ehrlich carcinoma (SEC) in mice. Eighty BALB/C mice were divided into four equal groups: SEC group, SEC+adriamycin, SEC+metformin, SEC+adriamycin+metformin. Tumor volume, survival rate, tissue catalase, tissue reduced glutathione, tissue malondialdehyde, tissue sphingosine kinase 1 activity, tissue caspase 3 activity and tissue tumor necrosis factor alpha were determined. A part of the tumor was examined for histopathological and immunohistochemical study. Adriamycin or metformin alone or in combination induced significant increase in the survival rate, tissue catalase, reduced glutathione and tissue caspase 3 activity with significant decrease in tumor volume, tissue malondialdehyde, tissue sphingosine kinase 1 activity and tumor necrosis factor alpha and alleviated the histopathological changes with significant increase in Trp53 expression and apoptotic index compared to SEC group. In conclusion, the combination of adriamycin and metformin had a better effect than each of these drugs alone against transplantable tumor model in mice.

摘要

阿霉素是一种细胞毒性蒽环类抗生素,用于治疗多种类型的癌症。二甲双胍是一种抗糖尿病药物,目前正在研究其对癌症的治疗作用。本研究的目的是探讨阿霉素和二甲双胍单独及联合应用对小鼠实体艾氏癌(SEC)的影响。将80只BALB/C小鼠分为四组,每组20只:SEC组、SEC+阿霉素组、SEC+二甲双胍组、SEC+阿霉素+二甲双胍组。测定肿瘤体积、生存率、组织过氧化氢酶、组织还原型谷胱甘肽、组织丙二醛、组织鞘氨醇激酶1活性、组织半胱天冬酶3活性和组织肿瘤坏死因子α。取部分肿瘤组织进行组织病理学和免疫组织化学研究。与SEC组相比,阿霉素或二甲双胍单独或联合应用均可显著提高生存率、组织过氧化氢酶、还原型谷胱甘肽和组织半胱天冬酶3活性,显著降低肿瘤体积、组织丙二醛、组织鞘氨醇激酶1活性和肿瘤坏死因子α,并减轻组织病理学变化,显著增加Trp53表达和凋亡指数。总之,与单独使用这两种药物相比,阿霉素和二甲双胍联合应用对小鼠移植性肿瘤模型的疗效更好。

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