不同药物敏感基因对人胰腺癌细胞PC-2的杀伤作用  

The killing effects of two prodrug sensitivity genes on human pancreatic carcinoma cells PC 2

作　　者：张雷[1] 刘彤华[1] 崔全才[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院病理科

出　　处：《中华病理学杂志》1998年第6期412-415,共4页Chinese Journal of Pathology

摘　　要：目的比较单纯疱疹病毒胸腺嘧啶核苷激酶（ＨＳＶＴＫ）／丙氧鸟苷（ＧＣＶ）和胞嘧啶脱氨基酶（ＣＤ）／５氟胞嘧啶（５ＦＣ）两系统对人胰腺癌ＰＣ２细胞的杀伤作用。方法构建表达ＨＳＶＴＫ和ＣＤ基因的重组逆转录病毒载体，将其直接导入胰腺癌细胞；噻唑蓝法检测转化细胞对前体药物的敏感度及５０％细胞受抑制时的药物浓度，即ＩＣ５０值，并对旁观者效应进行观察比较。结果ＨＳＶＴＫ基因转化细胞ＩＣ５０值为（１０６±０１２）μｍｏｌ／Ｌ，比未转化细胞下降５５８倍；ＣＤ基因转化细胞ＩＣ５０值为（３３００±０９５）μｍｏｌ／Ｌ，比未转化细胞下降２５８倍；混合细胞中含１０％的转化细胞时，ＨＳＶＴＫ／ＧＣＶ系统的生长抑制率为３９％，ＣＤ／５ＦＣ系统为５０３％。结论两系统对胰腺癌细胞ＰＣ２均有很好的杀伤和抑制细胞生长作用，ＨＳＶＴＫ／ＧＣＶ系统的治疗指数较高。Objective To compare the killing effects of herpes simplex virus thymidine kinase (HSV TK)/ganciclovir (GCV) system versus cytosine deaminase (CD)/5 flurocytosine (5 FC) system on human pancreatic carcinoma PC 2 cells. Methods Recombinant retroviral vectors expressing HSV TK and CD genes were constructed and transduced into pancreatic carcinoma cell line. Prodrug sensitivity and IC 50 values (concentration of drug at which cell growth is inhibited by 50%) of the transduced cells were measured by MTT method. The bystandser effects in the two systems were also compared. Results The IC 50 value of HSV TK transduced cells to GCV was (1.06±0.12)μmol/L and 558 fold lower than parental PC 2 cells, while the IC 50 value of CD transduced cells to 5 FC.00 was (33.00+0.95)μmol/L and 258 fold lower than parental PC 2 cells. Mixed cells containing 10% of transduced cells showed 39% and 50.3% growth inhibition in TK/GCV and CD/5 FC systems respectively. Conclusion Both HSV TK/GCV and CD/5 FC systems showed effecteive antitumor activity in vitro to pancreatic carcinoma PC 2 cells. The therapeutic index of HSV TK/GCV system is higher, but its bystander effect is lower than that of CD/5 FC system.

关 键 词：胰腺肿瘤 PC-2细胞 HSV-TK GCV CD 5-FC 

分 类 号：R735.9[医药卫生—肿瘤]