Forsythiae Fructus Inhibits B16 Melanoma Growth Involving MAPKs/Nrf2/HO-1 Mediated Anti-Oxidation and Anti-Inflammation

Forsythiae Fructus Inhibits B16 Melanoma Growth Involving MAPKs/Nrf2/HO-1 Mediated Anti-Oxidation and Anti-Inflammation
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DOI:
10.1142/s0192415x16500580
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发表时间:
2016-01-01
影响因子:
5.7
通讯作者:
He, Chengwei
He, Chengwei
中科院分区:
医学2区
文献类型:
--
作者:
Bao, Jiaolin;Ding, Renbo;He, Chengwei

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连翘(Forsythiae Fructus)为连翘(Forsythia suspensa(Thunb.)Vahl,在中文中的连翘,是传统中药(TCM)中最基本的草药之一。根据中医理论,它是典型的清热解毒药。本研究旨在探讨连翘水提物(FAE)对B16-F10黑色素瘤细胞的体内抗肿瘤作用。建立C57 BL/6小鼠B16-F10黑色素瘤移植瘤模型,观察FAE的体内抗肿瘤作用。FAE在体外对B16-F10细胞的生长有明显的抑制作用,在体内对肿瘤有明显的抑制作用。FAE能显著延长荷瘤小鼠的生存时间。FAE抑制肿瘤中的癌细胞增殖和血管生成,如Ki 67和CD 31表达降低所示。FAE处理组ROS、MDA、TNF-α和IL-6水平降低,GSH水平升高,表明FAE具有较强的抗氧化和抗炎活性。抗氧化蛋白Nrf-2和HO-1、肿瘤抑制因子P53和p-PTEN以及MAPK通路在肿瘤组织中的表达被FAE处理上调。这些数据表明,FAE在体外和体内对B16-F10小鼠黑色素瘤均表现出较强的抗肿瘤活性。FAE的抗肿瘤作用主要表现为降低肿瘤组织的氧化应激和炎症反应,这与FAE的清热解毒作用密切相关。
Forsythiae Fructus, the fruits of Forsythia suspensa (Thunb.) Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine (TCM). It is a typical heat-clearing and detoxicating herb, according to TCM theory. In this study, we investigated the antitumor effect of Forsythiae Fructus aqueous extract (FAE) on B16-F10 melanoma cells in vivo. The transplanted B16-F10 melanoma in C57BL/6 mice was established and used for the evaluation of the in vivo antitumor effect of FAE. FAE strongly inhibited the growth of B16-F10 cells in vitro and the tumor in vivo. The survival time of tumor-bearing mice was significantly prolonged by FAE. FAE inhibited cancer cell proliferation and angiogenesis in the tumor, as indicated by the decreased expressions of Ki67 and CD31. The levels of ROS, MDA, TNF-alpha and IL-6 decreased, while GSH increased in the FAE treatment group, indicating FAE possesses strong anti-oxidative and anti-inflammatory activity. The expression of anti-oxidant proteins Nrf-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by FAE treatment. These data demonstrated that FAE exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of FAE involved decreases in oxidative stress and inflammation in the tumor, which is closely related to the heat-clearing and detoxicating properties of FAE.