乏氧对黄酮类化合物放射增敏作用的实验性研究  

Research of Radiosensitizing Effect of Flavonoids under Hypoxia

作　　者：熊康萍 刘宏[1] 季可非 郭敏[1] 郭偲 周萌萌[1] 

机构地区：[1]广州军区武汉总医院药剂科,武汉430070 [2]湖北中医药大学药学院

出　　处：《中国药师》2016年第4期624-630,共7页China Pharmacist

基　　金：湖北省自然科学基金项目(编号:2014CFC1053)

摘　　要：目的:考察三种黄酮类化合物在乏氧条件下对卵巢癌SKOV3细胞的放射增敏效应。方法:将SKOV3细胞分为常氧组与乏氧组,建立体外SKOV3乏氧细胞模型并检测细胞内HIF-1α蛋白的水平加以验证;克隆形成法检测常氧与乏氧SKOV3细胞的放射敏感性;MTT法检测三种黄酮类化合物对SKOV3细胞增殖抑制的影响,筛选出药物的无毒浓度范围;改良的MTT法检测放射增敏效应,结合多靶单击模型拟合剂量存活曲线,分析放射生物学参数。结果:常氧组和乏氧组HIF-1α与β-Actin的灰度值之比分别为0.117和1.068,乏氧SKOV3细胞的放射敏感性显著低于常氧细胞;黄酮类化合物作用于SKOV3细胞的存活率随药物作用浓度的增大而降低;在常氧与乏氧条件下,随着药物浓度的增大,白杨素与槲皮素组D_0、D_q值显著减小(P<0.01),SER值显著增大(P<0.05)。灯盏花素各浓度组之间SER值无显著性差异(P>0.05)。乏氧组D_0、D_q、SER值整体高于常氧组。结论:乏氧诱导SKOV3细胞内HIF-1蛋白表达显著升高,导致细胞放射敏感性降低。白杨素与槲皮素可明显改善SKOV3细胞放射敏感性,且在乏氧条件下放射增敏效应更明显,而灯盏花素不具有此功效,其增敏机制可能是通过降低细胞内HIF-1α的水平和延迟细胞修复亚致死性损伤而实现。Objective： To investigate the radiosensitizing effect of three flavonoids on ovarian cancer SKOV3 cells under hypoxia.Methods： The SKOV3 cells were divided into normoxic group and hypoxic group. The hypoxic SKOV3 cellular model in vitro was established and tested by measuring the expression profile of HIF-1α protein in SKOV3 cells. Colony-forming assay was used to detect the radiosensitivity of normoxic and hypoxic SKOV3 cells. The cytotoxicity and radiosensitizing effects of flavonoids were evaluated on the basis of cell death and MTT assay.Results： The Western blot results showed that the gray intensity ratio of HIF-1α / β-Actin in hypoxia group was significantly higher than that in normoxia group（ 1.068 〉0.117）. Radiosensitivity of hypoxic SKOV3 cells in hypoxia group was significantly lower than that in normoxia group. The survival rate of SKOV3 cells was decreased with the increase of concentration.When the concentration was increased,D_0 and D_q in chrysin group and quercetin group were significantly decreased（ P 〈0.01）,and SER was increased（ P〈0.05）. SER showed no significant difference in breviscapine group（ P〉0.05）. The overall radiobiological parameters of hypoxia group were higher than those of normoxia group.Conclusion： Hypoxia can induce the expression of HIF-1α in SKOV3 cells,which results in the decrease of radiosensitivity. Chrysin and quercetin can enhance the radiosensitivity of SKOV3 cells,and the enhancement is significant under hypoxia,while breviscapine is without such effect. The radiosensitizing effect may be achieved by the level decrease of HIF-1α in SKOV3 cells and inhibition of DNA damage repair.

关 键 词：乏氧 肿瘤 SKOV3细胞株 黄酮 放射生物学 

分 类 号：R73-3[医药卫生—肿瘤]