中药复方羊鹤化瘀汤对实验性诱导乳腺癌发生的多靶点化学预防。
Multi-targeting chemoprevention of Chinese herb formula Yanghe Huayan decoction on experimentally induced mammary tumorigenesis.
机构信息
Department of breast surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, Shandong, China.
Shandong University of Traditional Chinese Medicine, Jinan, 250335, Shandong, China.
出版信息
BMC Complement Altern Med. 2019 Feb 13;19(1):48. doi: 10.1186/s12906-019-2456-1.
BACKGROUND
Development of safe and effective chemopreventive agents is a winning strategy in reducing the morbidity and mortality of breast cancer. The current study was to investigate the mechanism-based chemopreventive potential of a Chinese herb formula Yanghe Huayan (YHHY) Decoction on the classical 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinogenesis model.
METHODS
Female Sprague-Dawley rats at 42 days of age were orally administered with a human equivalent dose of YHHY Decoction at 0.02 ml/g (10 mg/ml) once daily, starting 1 wk. before and 4 wks following DMBA treatment. Mammary tumor occurrence was monitored every day. The length of time before palpable tumor is examined is defined as tumor-free survival time. High performance liquid chromatography (HPLC) analyses were adopted to identify major chemical compositions of the decoction. Following bioinformatics data mining and experimental analyses were performed to demonstrate the underlying mechanism of action.
RESULTS
DMBA animals receiving YHHY Decoction exhibited a significant delay (P = 0.014) and in some animals prevention (P = 0.046) of tumor occurrence without obvious toxicity. Oncogenic myc activation was significantly suppressed in the DMBA-induced rats by the YHHY treatment. Eight major chemical compositions of the decoction were identified and were shown to interfere with multiple tumorigenic pathways simultaneously in the mammary tumors, including inducing tumor apoptosis and up-regulating pro-apoptotic protein Bax and down-regulating anti-apoptotic protein Bcl-2; suppressing abnormal cell proliferation and the MAPK/ERK, PI3K/AKT signalings; blocking neo-angiogenesis and the VEGF/KDR signaling, and inhibiting oxidative stress in the mammary tumors.
CONCLUSION
The multi-components and multi-targeting properties of the YHHY Decoction support its use as a potent chemopreventive drug in breast cancer.
背景
开发安全有效的化学预防剂是降低乳腺癌发病率和死亡率的有效策略。本研究旨在探讨一种中药方剂“羊鹤化瘀”汤对经典的 7,12-二甲基苯并（a）蒽（DMBA）诱导的大鼠乳腺致癌模型的基于机制的化学预防潜力。
方法
42 日龄雌性 Sprague-Dawley 大鼠在 DMBA 处理前 1 周和处理后 4 周，每天口服给予与人等效剂量的“羊鹤化瘀”汤 0.02ml/g（10mg/ml）。每天监测乳腺肿瘤的发生情况。检测可触及肿瘤前的时间长度定义为无肿瘤存活时间。采用高效液相色谱（HPLC）分析方法鉴定汤的主要化学成分。随后进行生物信息学数据分析和实验分析，以证明其作用机制。
结果
接受“羊鹤化瘀”汤处理的 DMBA 动物的肿瘤发生明显延迟（P=0.014），在某些动物中甚至可以预防（P=0.046），且无明显毒性。“羊鹤化瘀”汤处理显著抑制了 DMBA 诱导大鼠中的致癌 myc 激活。该汤的 8 种主要化学成分被鉴定出来，并在乳腺肿瘤中同时干扰多种致癌途径，包括诱导肿瘤细胞凋亡和上调促凋亡蛋白 Bax，下调抗凋亡蛋白 Bcl-2；抑制异常细胞增殖及 MAPK/ERK、PI3K/AKT 信号通路；阻断新血管生成和 VEGF/KDR 信号通路，以及抑制乳腺肿瘤中的氧化应激。
结论
“羊鹤化瘀”汤的多成分、多靶点特性支持其作为一种有效的乳腺癌化学预防药物。
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