Zhang Wenting, Liu Bin, Feng Yaru, Liu Jie, Ma Zhiqiang, Zheng Jian, Xia Qing, Ni Yuanyuan, Li Farong, Lin Ruichao
Beijing Key Lab for Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
Beijing Key Lab for Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
J Ethnopharmacol. 2017 Jul 12;206:337-346. doi: 10.1016/j.jep.2017.05.033. Epub 2017 Jun 7.
Euphorbia pekinensis Rupr. (EP) is a Euphorbia species of Euphorbiaceae, which is widely used in traditional Chinese medicine. It has been reported to exhibit therapeutic effects on solid tumors, leukemias, and malignant ascites although underlying molecular mechanisms are poorly delineated. Anti-angiogenic therapy is a recognized strategy for treating cancer-based solid tumors, and is also associated with malignant ascites treatment.
To study the anti-angiogenic properties of the water extract of EP vinegar preparation (WEVEP).
Following WEVEP treatment, intersegmental blood vessels were assessed during the development of transgenic Tg (flk: mCherry) zebrafish as was the proliferation, migration and network formation of HUVECs in vitro. mRNA expression of specific angiogenic-related genes including VEGF family members, Met, and NRP2 was also measured using quantitative real-time PCR (Q-PCR).
Data demonstrated that angiogenesis was inhibited by the WEVEP in zebrafish (from 100µg/mL to 250µg/mL, p < 0.0001) and in the HUVEC model (from 100µg/mL to 400µg/mL, p < 0.0001). In the zebrafish model, the mean vessel numbers of administered groups were 26.00 ± 1.29 (100µg/mL), 24.54 ± 2.20 (150µg/mL), 22.66 ± 2.68 (200µg/mL), 20.80 ± 1.75 (250µg/mL), compared to 27.67 ± 0.96 of control group. Relative quantitative gene expression in zebrafish treated with WEVEP demonstrated that only VEGFR3 was significantly increased and other 23 genes including Met, VEGFA, Flt-1 were significantly decreased.
WEVEP can positively modulate angiogenesis via multiple targeting mechanisms. Our novel results contribute towards the discovery of a possible mechanism(s) of the traditional use of EP in the treatment of cancer and malignant ascites.
京大戟是大戟科大戟属的一种植物，在传统中药中广泛应用。据报道，它对实体瘤、白血病和恶性腹水具有治疗作用，但其潜在的分子机制尚不清楚。抗血管生成疗法是一种公认的治疗基于癌症的实体瘤的策略，也与恶性腹水的治疗相关。
研究京大戟醋制水提取物（WEVEP）的抗血管生成特性。
用WEVEP处理后，在转基因Tg（flk：mCherry）斑马鱼发育过程中评估节间血管，同时在体外评估人脐静脉内皮细胞（HUVECs）的增殖、迁移和网络形成。还使用定量实时PCR（Q-PCR）测量包括VEGF家族成员、Met和NRP2在内的特定血管生成相关基因的mRNA表达。
数据表明，WEVEP在斑马鱼中（从100μg/mL至250μg/mL，p<0.0001）和在HUVEC模型中（从100μg/mL至400μg/mL，p<0.0001）均抑制血管生成。在斑马鱼模型中，给药组的平均血管数量分别为26.00±1.29（100μg/mL）、24.54±2.20（150μg/mL）、22.66±2.68（200μg/mL）、20.80±1.75（250μg/mL），而对照组为27.67±0.96。用WEVEP处理的斑马鱼中的相对定量基因表达表明，只有VEGFR3显著增加，而包括Met、VEGFA、Flt-1在内的其他23个基因显著减少。
WEVEP可通过多种靶向机制正向调节血管生成。我们的新结果有助于发现京大戟在治疗癌症和恶性腹水中传统用途的可能机制。
