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红景天苷通过抑制炎症和促进细胞凋亡预防 DMBA/TPA 诱导的小鼠皮肤癌变。

Salidroside prevents skin carcinogenesis induced by DMBA/TPA in a mouse model through suppression of inflammation and promotion of apoptosis.

机构信息

Department of Dermatology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.

出版信息

Oncol Rep. 2018 Jun;39(6):2513-2526. doi: 10.3892/or.2018.6381. Epub 2018 Apr 18.

DOI:10.3892/or.2018.6381
PMID:29693192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5983924/
Abstract

Salidroside (SR) is a main component of Rhodiola rosea L. and exhibits a variety of pharmacologic properties. The present study was carried out to explore the potential effect of SR against skin cancer induced by 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13‑acetate (TPA) in female Institute for Cancer Research (ICR) mice and to reveal the underlying molecular targets regulated by SR. The mice were randomly divided into 4 groups: control, DMBA/TPA, DMBA/TPA+SR (20 mg/kg) and DMBA/TPA+SR (40 mg/kg). SR was administered to mice five times a week after DMBA treatments. In our study, we found that SR dose-dependently ameliorated skin cancer incidence and the multiplicity in the animal models by reducing the release of inflammation-related cytokines, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), cyclooxygenase 2 (COX2) and transforming growth factor β-1 (TGF-β1). Suppression of the nuclear factor (NF)-κB signaling pathway by SR was effective to prevent skin carcinogenesis. Furthermore, TUNEL analysis indicated that compared to the DMBA/TPA group, enhanced apoptosis was observed in the DMBA/TPA+SR group. In addition, p53 expression levels were increased by SR in the DMBA/TPA-induced mice. Therefore, SR was effective for inducing apoptosis during skin cancer progression triggered by DMBA/TPA. Consistently, p21, p53 upregulated modulator of apoptosis (PUMA), Bax and caspase-3 were highly induced by SR to enhance the apoptotic response for preventing skin cancer. Moreover, in vitro, we found that SR dramatically reduced the inflammatory response, while enhancing the aoptotic response by blocking NF-κB and activating caspase-3 pathways, respectively. In addition, flow cytometric analysis further confirmed the induction of apoptosis by SR in DMBA-treated cells in vitro. Taken together, the in vivo and in vitro studies illustrated that SR might be a promising compound to reduce skin cancer risk.

摘要

红景天苷（SR）是红景天的主要成分，具有多种药理作用。本研究旨在探讨 SR 对 7,12-二甲基苯并（a）蒽（DMBA）和 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的雌性 ICR 小鼠皮肤癌的潜在作用，并揭示 SR 调节的潜在分子靶点。将小鼠随机分为 4 组：对照组、DMBA/TPA 组、DMBA/TPA+SR（20mg/kg）组和 DMBA/TPA+SR（40mg/kg）组。在 DMBA 处理后，每周给小鼠给药 5 次。在我们的研究中，我们发现 SR 可通过减少炎症相关细胞因子的释放，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）、白细胞介素-6（IL-6）、环氧化酶-2（COX2）和转化生长因子-β-1（TGF-β1），从而剂量依赖性地改善动物模型中的皮肤癌发病率和多发性。SR 对核因子（NF）-κB 信号通路的抑制作用可有效预防皮肤癌发生。此外，TUNEL 分析表明，与 DMBA/TPA 组相比，DMBA/TPA+SR 组观察到增强的细胞凋亡。此外，SR 增加了 DMBA/TPA 诱导的小鼠中 p53 的表达水平。因此，SR 在 DMBA/TPA 诱导的皮肤癌进展过程中诱导细胞凋亡是有效的。一致地，p21、p53 上调凋亡调节剂（PUMA）、Bax 和 caspase-3 被 SR 高度诱导，以增强凋亡反应以预防皮肤癌。此外，体外实验表明，SR 通过分别阻断 NF-κB 和激活 caspase-3 途径，显著降低炎症反应，同时增强凋亡反应。此外，流式细胞术分析进一步证实了 SR 在体外 DMBA 处理细胞中诱导的细胞凋亡。总之，体内和体外研究表明，SR 可能是一种有前途的化合物，可降低皮肤癌风险。

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