Hu Y-Q, Wang J, Wu J-H
Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai, P.R. China.
Eur Rev Med Pharmacol Sci. 2016 Jul;20(13):2935-46.
Resveratrol (RES), present in fruits and plants, is a natural compound that has been shown various medicinal properties, including protection of cardiovascular disease and cancer risk. However, the effects of RES on skin cancer have not been investigated. The present work was designed to explore the anticancer potential of RES against chemical-induced skin carcinogenesis in rats.
Skin carcinogenesis were induced in male Wistar rats by a single topical application of 7,12-dimethylbenz(a)anthracene (DMBA) and 2 weeks later, 12-O-tetradecanoylphorbol-13-acetate (TPA) were topically applied thrice a week to promote skin carcinogenesis. RES at a dose of 1 or 2 mg/kg body weight/week were administered to DMBA treated rats. The effects of RES on DMBA-modified cell-cycle arrest, apoptosis and protein expressions were analyzed by flow cytometry, immunohistochemistry and Western blot, respectively.
RES treatment caused a significant reduction of DMBA-induced tumor occurrence, tumor volume and tumor weight, as compared to DMBA control group. Further, RES treatment increases G2/M arrest and apoptosis by modulating cell-cycle and apoptosis regulated genes such as p53, p21, caspase-3, bax, survivin, cyclin-B and cdc-2 when compared with DMBA control group.
Taken together, the anticancer effect of RES is associated with regulation of cell-cycle and apoptosis in skin cancer, thereby attenuating skin cancer growth. Hence, these findings suggest that RES may be a therapeutic agent for skin cancer treatment.
白藜芦醇（RES）存在于水果和植物中，是一种天然化合物，已显示出多种药用特性，包括对心血管疾病的保护作用和降低癌症风险。然而，RES对皮肤癌的影响尚未得到研究。本研究旨在探讨RES对大鼠化学诱导皮肤癌发生的抗癌潜力。
通过单次局部应用7,12-二甲基苯并(a)蒽（DMBA）诱导雄性Wistar大鼠发生皮肤癌，2周后，每周3次局部应用12-O-十四酰佛波醇-13-乙酸酯（TPA）以促进皮肤癌发生。将剂量为1或2mg/kg体重/周的RES给予经DMBA处理的大鼠。分别通过流式细胞术、免疫组织化学和蛋白质印迹分析RES对DMBA诱导的细胞周期阻滞、细胞凋亡和蛋白质表达的影响。
与DMBA对照组相比，RES处理导致DMBA诱导的肿瘤发生率、肿瘤体积和肿瘤重量显著降低。此外，与DMBA对照组相比，RES处理通过调节细胞周期和凋亡调节基因如p53、p21、半胱天冬酶-3、bax、生存素、细胞周期蛋白-B和细胞分裂周期蛋白2，增加了G2/M期阻滞和细胞凋亡。
综上所述，RES的抗癌作用与皮肤癌中细胞周期和细胞凋亡的调节有关，从而减弱皮肤癌的生长。因此，这些发现表明RES可能是一种治疗皮肤癌的药物。
