二甲双胍预处理增强多柔比星对乳腺癌的增殖抑制作用。
Metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.
机构信息
Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, 382481, India.
出版信息
Ann Pharm Fr. 2023 Jun;81(4):636-652. doi: 10.1016/j.pharma.2023.03.001. Epub 2023 Mar 11.
OBJECTIVES
The present study aimed to evaluate the effect of metformin pretreatment on the potentiation of antiproliferative action of doxorubicin against breast cancer.
MATERIAL AND METHODS
Female Wistar rats were administered with 7,12-Dimethylbenz(a)anthracene (DMBA) (35mg) in 1mL olive oil subcutaneously beneath the mammary gland. Animals were pretreated with metformin (Met) 200mg/kg two weeks before DMBA administration. DMBA control groups received doxorubicin (Dox) (4mg/kg and 2mg/kg), Met (200mg/kg) alone and in combination with Dox (4mg/kg). Met pre-treated DMBA control groups received Dox 4mg/kg and 2mg/kg.
RESULTS
Met pre-treated groups treated with Dox exhibited a decrease in tumor incidence, tumor volume and increased survival rate than the DMBA group. Organ-to-body weight ratios and histopathology of heart, liver and lungs of Met pre-treated groups treated with Dox showed lesser toxicity than Dox treated DMBA control groups. There was a noteworthy decrease in malondialdehyde levels and a substantial increase in the levels of reduced glutathione together with a significant decrease in the levels of inflammatory markers like IL-6, IL-1β and NF-κB in Met pre-treated groups treated with Dox. Histopathology of breast tumors revealed better control of tumors in Met pre-treated groups treated with Dox than DMBA control group. Immunohistochemistry and real-time PCR data revealed a significant reduction in Ki67 expression in Met pre-treated groups treated with Dox as compared to the DMBA control group.
CONCLUSION
The present study suggests that metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.
目的
本研究旨在评估二甲双胍预处理对增强多柔比星对乳腺癌增殖抑制作用的影响。
材料和方法
雌性 Wistar 大鼠皮下注射 7,12-二甲基苯并蒽（DMBA）（35mg）于乳腺下 1ml 橄榄油中。动物在 DMBA 给药前两周用二甲双胍（Met）200mg/kg 预处理。DMBA 对照组分别接受多柔比星（Dox）（4mg/kg 和 2mg/kg）、Met（200mg/kg）单独和联合 Dox（4mg/kg）治疗。Met 预处理 DMBA 对照组接受 Dox 4mg/kg 和 2mg/kg。
结果
与 DMBA 组相比，用 Dox 处理的 Met 预处理组肿瘤发生率、肿瘤体积降低，生存率增加。用 Dox 处理的 Met 预处理组的器官/体重比值和心、肝、肺的组织病理学显示出比 Dox 处理的 DMBA 对照组更小的毒性。用 Dox 处理的 Met 预处理组的丙二醛水平显著降低，还原型谷胱甘肽水平显著升高，IL-6、IL-1β 和 NF-κB 等炎症标志物水平显著降低。乳腺肿瘤的组织病理学显示，用 Dox 处理的 Met 预处理组对肿瘤的控制要好于 DMBA 对照组。免疫组化和实时 PCR 数据显示，与 DMBA 对照组相比，用 Dox 处理的 Met 预处理组 Ki67 表达显著降低。
结论
本研究表明，二甲双胍预处理增强了多柔比星对乳腺癌的增殖抑制作用。
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