Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.
Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey.
Expert Opin Ther Targets. 2020 Feb;24(2):155-162. doi: 10.1080/14728222.2020.1724961. Epub 2020 Feb 5.
: The purpose of the present study was to examine the chemopreventive effect of stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced murine breast cancer model.: Groups of 20 female mice were challenged with the DMBA. DMBA-challenged mice were assigned to various chemoprevention treatments, including stampidine, paclitaxel, and stampidine plus paclitaxel according to the same treatment schedules for 25 weeks.: Stampidine resulted in substantially reduced numbers of tumors, tumor weight as well as tumor size in DMBA-treated mice. Stampidine was as effective as paclitaxel in the model and their combination exhibited greater chemopreventive activity, as measured by reduced tumor incidence and improved tumor-free survival as well as overall survival of DMBA-treated mice. The length of time for the initial tumor to appear in DMBA-challenged mice treated with stampidine was longer than that of mice treated DMBA-challenged control mice. Tumors from mice treated with stampidine or stampidine plus paclitaxel displayed unique changes of a signature protein cassette comprised BRCA1, p21, Bax, and Bcl-2.: Stampidine has potent chemopreventive activity and is as effective as the standard chemotherapy drug paclitaxel in the chemical carcinogenesis.
本研究的目的是检测 2'-脱氧-5-氟胞苷芳基膦酸酯(stampidine)的化学预防作用,并与标准抗癌药物紫杉醇进行对比,在成熟的 7,12-二甲基苯并(a)蒽(DMBA)诱导的小鼠乳腺癌模型中进行研究。
20 只雌性小鼠被 DMBA 攻击。DMBA 攻击的小鼠被分配到各种化学预防治疗组,包括 stampidine、紫杉醇和 stampidine 加紫杉醇,根据相同的治疗方案进行 25 周治疗。
Stampidine 导致 DMBA 处理的小鼠肿瘤数量、肿瘤重量和肿瘤大小明显减少。Stampidine 在该模型中与紫杉醇一样有效,它们的组合表现出更强的化学预防活性,表现为减少肿瘤发生率、改善肿瘤无生存以及 DMBA 处理的小鼠的总生存。用 stampidine 处理的 DMBA 攻击的小鼠中初始肿瘤出现的时间比用 DMBA 处理的对照小鼠长。用 stampidine 或 stampidine 加紫杉醇治疗的肿瘤显示出 BRCA1、p21、Bax 和 Bcl-2 组成的特征蛋白盒的独特变化。
Stampidine 具有很强的化学预防活性,与标准化疗药物紫杉醇在化学致癌作用中同样有效。