摘要
目的 探讨祁州漏芦提取物(Rhaponticum uniflorum extract, RUE)对小鼠H22移植瘤血管生成及细胞凋亡的影响。方法 建立H22肝癌皮下移植瘤小鼠模型,随机分为模型组、祁州漏芦提取物高、中、低剂量组和氟尿嘧啶组。连续干预10 d。采用苏木素-伊红(HE)染色法观察肿瘤组织病理学变化,采用DNA ladder法检测肿瘤细胞凋亡情况,采用免疫组织化学法检测肿瘤组织内微血管密度(microvessel density, MVD),采用免疫印迹法检测肿瘤组织血管内皮生长因子(vascular endothelial growth factor, VEGF)、血管内皮细胞生长因子受体2(vascular endothelial growth factor receptor 2, VEGFR2)和缺氧诱导因子-1α(hypoxia inducible factor-1α, HIF-1α)的蛋白表达。结果 与模型组比较,祁州漏芦提取物组肿瘤细胞生长受抑,坏死程度较严重;DNA梯形条带显著增多;肿瘤组织微血管密度显著降低;血管内皮生长因子、血管内皮生长因子受体2和缺氧诱导因子-1α蛋白的表达均显著降低。结论 祁州漏芦提取物对H22移植瘤小鼠具有抑制血管生成和诱导细胞凋亡作用,其抗血管生成作用可能与下调移植瘤组织血管内皮生长因子、缺氧诱导因子-1α、血管内皮生长因子受体2的蛋白表达有关。
Abstract
OBJECTIVE To investigate the effects of Rhaponticum uniflorum extract (RUE) on angiogenesis and apoptosis of H22 transplanted tumor tissue in mice. METHODS Mice bearing H22 hepatoma cells were randomly assigned into 5 groups: model, high, medium and low dose RUE, and 5-fluorouracil (5-Fu) group. The intervention was lasted for 10 d. The pathological changes were detected with hematoxylin & eosin (HE) staining, the apoptosis of hepatoma cells were determined by DNA laddering method, the microvessel densities (MVD) were detected using immunohistochemical assay, and the protein expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2) and hypoxia-inducible factor-1α (HIF-1α) were detected by Western blot method. RESULTS RUE treatment reduced the cell proliferation, aggravated the necrosis of transplanted tumor tissue, reduced DNA fragmentation of H22 hepatoma cells, decreased MVD of tumor tissue, and down-regulated the protein expression of VEGF, VEGFR2 and HIF-1α of the transplanted tumor tissue, as compared with the model group. CONCLUSION RUE could exhibit anti-angiogenic and pro-apoptotic effects against H22 hepatoma cells in mice, and its anti-angiogenic mechanism is probably related to down-regulation of VEGF, VEGFR2 and HIF-1α proteins.
关键词
漏芦 /
H22 /
抗血管生成 /
诱导细胞凋亡
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Key words
Rhaponticum uniflorum /
H22 /
anti-angiogenesis /
pro-apoptosis
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金爱花,高峰,许惠仙,全吉淑.
祁州漏芦对小鼠H22移植瘤血管生成及细胞凋亡的影响[J]. 中国药学杂志, 2016, 51(4): 280-283 https://doi.org/10.11669/cpj.2016.04.007
JIN Ai-hua, GAO Feng, XU Hui-xian, QUAN Ji-shu.
Effects of Rhaponticum uniflorum on Angiogenesis and Apoptosis of H22 Transplanted Tumor Tissue in Mice[J]. Chinese Pharmaceutical Journal, 2016, 51(4): 280-283 https://doi.org/10.11669/cpj.2016.04.007
中图分类号：
R285.5
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参考文献
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脚注
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基金
国家自然科学基金资助项目(81160539)
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