Multi-targeting chemoprevention of Chinese herb formula Yanghe Huayan decoction on experimentally induced mammary tumorigenesis
Multi-targeting chemoprevention of Chinese herb formula Yanghe Huayan decoction on experimentally induced mammary tumorigenesis
复制标题
中药阳和化炎汤对实验性乳腺肿瘤的多靶点化学预防
DOI：
10.1186/s12906-019-2456-1
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发表时间：
2019-02-13
影响因子：
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通讯作者：
Li, Xiangqi
中科院分区：
文献类型：
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作者：
Li, Jingwei;Liu, Xiaofei;Li, Xiangqi
背景：开发安全有效的化学预防药物是降低乳腺癌发病率和死亡率的一种成功策略。本研究旨在基于机制探讨中药方剂阳和化岩（YHHY）汤对经典的7,12 - 二甲基苯并（a）蒽（DMBA）诱导的大鼠乳腺肿瘤发生模型的化学预防潜力。
方法：42日龄的雌性Sprague - Dawley大鼠在DMBA处理前1周开始，每日口服一次人等效剂量为0.02ml/g（10mg/ml）的YHHY汤，持续至DMBA处理后4周。每天监测乳腺肿瘤的发生情况。将可触及肿瘤出现之前的时间长度定义为无瘤生存时间。采用高效液相色谱（HPLC）分析来鉴定该汤剂的主要化学成分。随后进行生物信息学数据挖掘和实验分析以阐明其潜在作用机制。
结果：接受YHHY汤的DMBA处理动物表现出肿瘤发生显著延迟（P = 0.014），部分动物肿瘤发生得到预防（P = 0.046），且无明显毒性。YHHY治疗显著抑制了DMBA诱导的大鼠中致癌基因myc的激活。鉴定出该汤剂的8种主要化学成分，它们在乳腺肿瘤中同时干扰多种致瘤途径，包括诱导肿瘤细胞凋亡，上调促凋亡蛋白Bax并下调抗凋亡蛋白Bcl - 2；抑制异常细胞增殖以及MAPK/ERK、PI3K/AKT信号通路；阻断新生血管生成以及VEGF/KDR信号通路，并抑制乳腺肿瘤中的氧化应激。
结论：YHHY汤的多成分和多靶点特性支持其作为一种有效的乳腺癌化学预防药物使用。
BackgroundDevelopment 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.MethodsFemale 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.ResultsDMBA 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.ConclusionThe multi-components and multi-targeting properties of the YHHY Decoction support its use as a potent chemopreventive drug in breast cancer.