白藜芦醇增强5-氨基酮戊酸在人脑胶质瘤细胞中的光动力治疗作用  

Enhancement of resveratrol to 5-aminolevulinic acid in human glioma cells by photodynamic therapy

作　　者：孙伟[1] 刘卫东[1] 龚良[1] 刘向阳[1] 郑佳佳[1] 钱忠心[1] SUN Wei;LIU Wei-dong;GONG Liang(Department of Neurosurgery,Punan Hospital,Pudong New District,Shanghai 200125,China)

机构地区：[1]上海市浦东新区浦南医院神经外科,上海200125

出　　处：《临床神经外科杂志》2019年第1期23-28,共6页Journal of Clinical Neurosurgery

基　　金：上海市浦东新区科委项目(PKJ2015-Y25);上海市医学重点专科建设(ZK2015A12);上海市浦东新区卫生系统临床高原学科建设项目(PWYgy2018-04)

摘　　要：目的研究白藜芦醇不但具有直接治疗脑胶质瘤的作用,而且作为一种ABCG2抑制剂,可以通过抑制BCRP/ABCG2,影响原卟啉Ⅸ(PpⅨ)排出细胞。探讨白藜芦醇增强对于经5-氨基酮戊酸(5-ALA)处理过的人脑胶质瘤细胞的光治疗(PDT)效果。方法 4种恶性脑胶质瘤细胞系(U87MG,U251,A172和T98G)在和不同浓度(0. 01～1. 0μmol/L)的白藜芦醇作用之前,与5-ALA(1 mmol/L)相互作用。测定白藜芦醇对细胞内外的PpⅨ水平,BCRP/ABCG2 mRNA和ABCG2蛋白的表达,以及体外PDT的效果。结果0. 1μmol/L或更高浓度的白藜芦醇,可以提高恶性脑胶质瘤细胞内的PpⅨ水平,在所有4种细胞系均呈药物剂量依赖性。白藜芦醇不但可以降低BCRP/ABCG2 mRNA的表达水平,而且可以减少细胞膜上BCRP/ABCG2蛋白的表达;并且有效地提高恶性脑胶质瘤细胞PDT的效果。结论白藜芦醇不但可以抑制BCRP/ABCG2介导的恶性脑胶质瘤细胞内PpⅨ的外流,并且可以增加细胞内的PpⅨ的含量,从而达到提高PDT的效果。Objective To study the effect of resveratrol not only on the direct treatment of human glioma cells,but also on the excretion of protoporphyrinⅨ(PpⅨ)from living cells by inhibiting BCRP/ABCG2 as an ABCG2 inhibitor and to evaluate the effect of resveratrol on 5-aminolevulinic acid(5-ALA)treated human glioma cells.The effect of photodynamic therapy(PDT)was evaluated.Methods Four malignant glioma cell lines(U87MG,U251,A172 and T98G)interacted with 5-ALA(1 mM)before mix with resveratrol at different concentrations(0.01-1.0μM).To study the effect of resveratrol on intracellular PpⅨ,the expression of BCRP/ABCG2 mRNA and ABCG2 protein,and the PDT in vitro.Results Resveratrol at 0.1μM or higher concentration could increase the level of PpⅨin malignant brain tumor cells,which was dose-dependent in all four cell lines studied.Resveratrol not only decreased the expression of BCRP/ABCG2 mRNA,but also decreased the expression of BCRP/ABCG2 protein on cell membrane,and effectively improved the effect of photodynamic therapy for malignant brain tumors.Conclusion Resveratrol can not only inhibit the outflow of PpⅨin malignant brain tumor cells mediated by BCRP/ABCG2,but also increase the content of PpⅨin cells,so as to improve the efficacy of PDT.

关 键 词：5-氨基酮戊酸 白藜芦醇 原卟啉Ⅸ 光动力治疗 

分 类 号：R739.41[医药卫生—肿瘤]