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1,4-二氢吡啶对 DMBA 诱导的小鼠皮肤肿瘤模型的抗癌活性。

Anticancer activity of a 1,4-dihydropyridine in DMBA-induced mouse skin tumor model.

机构信息

Department of Biochemistry and Biophysics, University of Kalyani, Kalyani.

Department of Veterinary Pharmacology and Toxicology, West Bengal University of Animal & Fishery Sciences, Mohanpur, Nadia, West Bengal.

出版信息

Anticancer Drugs. 2020 Apr;31(4):394-402. doi: 10.1097/CAD.0000000000000887.

DOI:10.1097/CAD.0000000000000887
PMID:32011364
Abstract

Antitumor potential of a 1,4-dihydropyridine derivative (DHP-8) has been successfully studied previously in a number of cancer cell lines including the human melanoma cells, A375. In order to validate its anticancer activity, DMBA induced tumor in Swiss Albino mice was considered for this study. DMBA causes skin carcinoma in murine systems and is an important in vivo model for evaluating the efficacy of any new chemical entity against skin cancer. Topical administration of DHP-8 at the dose rate of 33.3 and 50.0 mg/kg body weight showed a significant reduction in tumor parameters. It also prevented the progression and differentiation of squamous cell carcinoma, as evidenced from histopathological studies. Immunohistochemical analysis for the expression of Ki67 indicated that it also reduced cancer cell proliferation. Additionally, it induced apoptosis in the tumor cells by activation of Caspase3. Our results indicated that DHP-8 efficiently attenuated DMBA induced tumor progression and it could be a potent therapeutic agent for skin cancer treatment.

摘要

先前已有研究表明,1,4-二氢吡啶衍生物(DHP-8)在多种癌细胞系中具有抗肿瘤潜力,包括人黑色素瘤细胞 A375。为了验证其抗癌活性,本研究选择了 DMBA 诱导的瑞士白化病小鼠肿瘤模型。DMBA 在鼠类系统中会引起皮肤癌,是评估任何新化学实体对皮肤癌疗效的重要体内模型。以 33.3 和 50.0mg/kg 体重的剂量给予 DHP-8 进行局部给药,可显著降低肿瘤参数。它还可以预防鳞状细胞癌的进展和分化,这可以从组织病理学研究中得到证明。Ki67 的免疫组织化学分析表明,它还可以减少癌细胞增殖。此外,它通过激活 Caspase3 诱导肿瘤细胞凋亡。我们的结果表明,DHP-8 可有效抑制 DMBA 诱导的肿瘤进展,有望成为皮肤癌治疗的有效治疗药物。

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