己酮可可碱对人肝癌HepG2细胞的放射增敏作用及其作用机制  

Radiosensitization by pentoxifylline in human hepatoma cell line HepG2 and its mechanism

作　　者：吴德华[1] 刘莉[2] 陈龙华[1] 

机构地区：[1]第一军医大学南方医院放疗科,广东广州510515 [2]第一军医大学南方医院放疗科病理科,广东广州510515

出　　处：《第一军医大学学报》2004年第4期382-385,共4页Journal of First Military Medical University

基　　金：广东省自然科学基金重点项目(013056)~~

摘　　要：目的研究己酮可可碱(pentoxifylline, PTX)对人肝癌HepG2细胞的放射增敏作用并初步探讨其作用机制。方法应用MTT法检测PTX药物毒性实验,用克隆形成实验观察PTX对放射敏感性的影响,用流式细胞仪(FCM)技术分析X射线照射对HepG2细胞周期分布和PTX对放射引起的细胞周期阻滞的影响。结果不同浓度的PTX作用于肝癌HepG2细胞24 h后,其细胞毒性呈剂量依赖性,最适浓度为2 mmol/L。PTX能显著降低放射后HepG2细胞的克隆形成率,其放射增敏比为1.31±0.16。单纯照射组照射可以导致HepG2细胞G2期阻滞,单纯照射组及照射6 Gy加2 mmol/L PTX组的细胞20 h G2-M期比例分别为32.15%和19.52%,PTX能够去除放射引起的HepG2细胞G2期阻滞。结论PTX对HepG2细胞有放射增敏作用,其机制可能与PTX去除放射引起的G2期阻滞等因素有关。Objective To investigate the radiosensitization by pentoxifylline (PTX) in human hepatoma cell line HepG2 and its possible mechanism. Methods MTT assay was used to evaluate the cytotoxicity of PTX and clonogenic assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). Flow cytometry was performed to observe the changes in the cell cycle of HepG2 cells in response to X-ray irradiation and the effect of PTX intervention. Results The cytotoxicity of PTX increased in a dose-dependent manner following a 24-hour treatment, with the optimal dose range of 1-5 mmol/L. A sub-toxic dose of PTX at 2 mmol/L was used in the subsequent experiments. PTX significantly reduced the clonogenic activity and enhanced the radiosensitivity of HepG2 cells with a SER of 1.3±0.16 at the dose of 2 mmol/L. Irradiation resulted in cell cycle arrest at G 2 phase in HepG2 cells, and the percentages of HepG2 cells in G 2 -M phase were 32.15% and 19.52% respectively after exposure to 6 Gy radiation alone and to 6 Gy plus 2 mmol/L PTX at 20 h, demonstrating the effectiveness of PTX in resolving radiation-induced G 2 arrest. Conclusion Radiosen- sitization by PTX is possibly associated with the abrogation of G 2 arrest in HepG2 cells following radiation exposure.

关 键 词：己酮可可碱 肝癌 HEPG2细胞 放射增敏作用 作用机制 

分 类 号：R735.7[医药卫生—肿瘤]