Protective effects of silymarin against photocarcinogenesis in a mouse skin model
Protective effects of silymarin against photocarcinogenesis in a mouse skin model
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DOI：
10.1093/jnci/89.8.556
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发表时间：
1997-04-16
影响因子：
10.3
通讯作者：
Agarwal, R
中科院分区：
文献类型：
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作者：
Katiyar, SK;Korman, NJ;Agarwal, R
背景：非黑色素瘤皮肤癌是人类最常见的癌症；太阳紫外线是其主要原因。因此，确定能够预防这种癌症的药物是很重要的。目的：研究水飞蓟素（一种从水飞蓟植物中分离出来的类黄酮化合物）对UVB辐射诱导的小鼠非黑色素瘤皮肤癌的保护作用，并探讨其作用机制。方法：在长期研究中，采用三种不同的治疗方案，每种方案评估水飞蓟素在不同癌变阶段的保护作用。雌性SKH-1无毛小鼠分别经历了：1)uvb诱导的肿瘤起始，随后是酚酯介导的肿瘤促进；2)7,12-二甲基苯[a]蒽诱导的肿瘤起始，随后是uvb介导的肿瘤促进；3)uvb诱导的完全致癌。每个方案使用40只小鼠，分为对照组和实验组。在UVB照射前，以每次9mg的剂量局部应用水飞蓟素，并评估其对肿瘤发生率（肿瘤小鼠的百分比）、肿瘤多样性（每只小鼠的肿瘤数量）和每只小鼠的平均肿瘤体积的影响。在短期研究中，测量了以下参数：晒伤和凋亡细胞的形成，皮肤水肿，表皮过氧化氢酶和环氧化酶（COX）活性，以及鸟氨酸脱羧酶（ODC）的酶活性和信使RNA （mRNA）表达，ODC是肿瘤促进阶段经常观察到的标志物。肿瘤发生率差异采用Fisher精确检验，肿瘤多样性和肿瘤体积采用双样本Wilcoxon秩和检验，其他测量均采用Student’st检验。所有统计检验均为双侧检验。结果：在uvb诱导的肿瘤起始方案中，水飞蓟素治疗使肿瘤发生率从40%降低到20% (P = 0.30)，肿瘤多样性降低67% (P = 0.10)，每只小鼠肿瘤体积降低66% （P = 0.14）。在uvb诱导的肿瘤促进方案中，水飞蓟素治疗将肿瘤发生率从100%降低到60% (P
Background: Nonmelanoma skin cancer is the most common cancer among humans; solar UV is its major cause. Therefore, it is important to identify agents that can offer protection against this cancer. Purpose: We evaluated the protective effects of silymarin, a flavonoid compound isolated from the milk thistle plant, against UVB radiation-induced nonmelanoma skin cancer in mice and delineated the mechanism(s) of its action. Methods: For long-term studies, three different protocols of treatment were employed, each evaluating protection by silymarin at a different stage of carcinogenesis. Female SKH-1 hairless mice were subjected to 1) UVB-induced tumor initiation followed by phorbol ester-mediated tumor promotion, 2) 7,12-dimethylbenzl[a]anthracene-induced tumor initiation followed by UVB-mediated tumor promotion, and 3) UVB-induced complete carcinogenesis. Forty mice were used in each protocol and were divided into control and treatment groups. Silymarin was applied topically at a dose of 9 mg per application before UVB exposure, and its effects on tumor incidence (% of mice with tumors), tumor multiplicity (number of tumors per mouse), and average tumor volume per mouse were evaluated. In short-term studies, the following parameters were measured: formation of sunburn and apoptotic cells, skin edema, epidermal catalase and cyclooxygenase (COX) activities, and enzymatic activity and messenger RNA (mRNA) expression for ornithine decarboxylase (ODC), a frequently observed marker at tumor promotion stage. Fisher's exact test was used to evaluate differences in tumor incidence, two-sample Wilcoxon rank sum test was used for tumor multiplicity and tumor volume, and Student's t test was used for all other measurements. All statistical tests were two-sided. Results: In the protocol with UVB-induced tumor initiation, silymarin treatment reduced tumor incidence from 40% to 20% (P =.30), tumor multiplicity by 67% (P =.10), and tumor volume per mouse by 66% (P =.14). In the protocol with UVB-induced tumor promotion, silymarin treatment reduced tumor incidence from 100% to 60% (P