| 张弛,张曲,杨曦,等.黄连素对乏氧环境中鼻咽癌放射增敏作用机制的研究[J].中华放射医学与防护杂志,2014,34(9):663-667.,et al.Mechanism of radiosensitization effect of berberine on human nasopharyngeal carcinoma in hypoxia[J].Chin J Radiol Med Prot,2014,34(9):663-667 |
| 黄连素对乏氧环境中鼻咽癌放射增敏作用机制的研究 |
| Mechanism of radiosensitization effect of berberine on human nasopharyngeal carcinoma in hypoxia |
| 投稿时间：2013-10-27 |
| DOI：10.3760/cma.j.issn.0254-5098.2014.09.005 |
| 中文关键词: 黄连素 鼻咽癌 乏氧 放射增敏 乏氧诱导因子 |
| 英文关键词:Berberine Nasopharyngeal carcinoma Hypoxia Radiosensitivity Hypoxia induced factor |
| 基金项目:江苏省2012年度普通高校研究生科研创新计划项目（CXZZ12_0588） |
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| 中文摘要: |
| 目的 探究黄连素对乏氧环境中鼻咽癌细胞系CNE-2及裸鼠移植瘤的增敏效应及其分子机制。方法 四甲基偶氮唑盐比色法（MTT法）检测黄连素对CNE-2细胞的增殖抑制作用，克隆形成实验观察5 μmol/L黄连素对常氧和乏氧环境中CNE-2细胞放射敏感性的影响。黄连素乏氧下作用24 h后给予8 Gy X射线照射，流式细胞技术检测CNE-2细胞凋亡率。建立鼻咽癌CNE-2细胞裸鼠移植瘤模型，观察黄连素及单次8 Gy照射对移植瘤的抑制作用。Western blot检测乏氧条件下黄连素对HIF-1α及VEGF蛋白表达的抑制作用。 结果 黄连素显著抑制CNE-2细胞增殖，且存在时间、浓度依赖效应，24 h药物作用后半数抑制剂量IC50为（14.9±2.2）μmol/L。乏氧环境下，5 μmol/L黄连素处理后的克隆形成率较单纯乏氧组下降，其增敏比（SERD0）为1.27。在常氧环境中克隆形成率较乏氧组显著增加，常氧组和常氧加药组的SERD0分别为1.45和1.74。5和15 μmol/L黄连素能在乏氧环境中单独发挥促凋亡作用，与对照组比较差异有统计学意义（t=5.01、9.02，P<0.05），黄连素联合照射后，凋亡率较单纯照射组增加（t=5.31、9.91，P<0.05）。 体内实验显示，照射给药组肿瘤体积的增长显著延迟于对照组及单纯给药组，肿瘤倍增时间联合组较单纯照射组及对照组差异有统计学意义（t=2.96、14.52，P<0.05）。Western blot显示乏氧条件下HIF-1α、VEGF表达升高，黄连素作用24 h后表达显著下调。结论 黄连素对乏氧环境中的CNE-2细胞及裸鼠移植瘤有放射增敏作用，其与下调乏氧环境中HIF-1α及下游因子VEGF的表达有关。 |
| 英文摘要: |
| Objective To investigate the radiosensitiation effect of berberine on human nasopharyngeal carcinoma (NPC) in hypoxia condition and explore the underlying mechanisms.Methods MTT assay, clonogenic assay and flow cytometry were performed to analyze cell proliferation, colony formation and apoptosis, respectively. Male nude mice inoculated subcutaneously with CNE-2 cells were used to examine the radiosensitization effect of berberine in vivo. The expressions of HIF-1α and VEGF were assessed by Western blot.Results Berberine efficiently inhibited the proliferation of CNE-2 cells in time-dependent and dose-dependent fashions with an IC50 of (14.9±2.2) μmol/L. Clonogenic survival assay showed that berberine (5 μmol/L) sensitized CNE-2 cells to ionizing radiation in hypoxia and its SERD0 was 1.27. Under hypoxic condition, berberine alone (5, 15 μmol/L) could induce apoptosis (t=5.01, 9.02,P<0.05) and it further promoted 8 Gy radiation-induced apoptosis (t=5.31, 9.91,P<0.05). Moreover, berberine significantly delayed the tumor growth in the combination group (berberine + irradiation) compared with the mice received irradiation alone or PBS (t=2.96, 14.52, P<0.05). Immunobloting assay showed that berberine inhibited the upregulation of HIF-1α and VEGF induced by hypoxia in CNE-2 cells.Conclusion Berberine confers radiosensitivity on hypoxic NPC in vitro and in vivo, which is probably associated with the downregulation of HIF-1α and VEGF expressions. |
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