摘要
目的比较单纯疱疹病毒胸腺嘧啶核苷激酶（ＨＳＶＴＫ）／丙氧鸟苷（ＧＣＶ）和胞嘧啶脱氨基酶（ＣＤ）／５氟胞嘧啶（５ＦＣ）两系统对人胰腺癌ＰＣ２细胞的杀伤作用。方法构建表达ＨＳＶＴＫ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ＨＳＶＴＫ基因转化细胞ＩＣ５０值为（１０６±０１２）μｍｏｌ／Ｌ，比未转化细胞下降５５８倍；ＣＤ基因转化细胞ＩＣ５０值为（３３００±０９５）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，ＨＳＶＴＫ／ＧＣＶ系统的生长抑制率为３９％，ＣＤ／５ＦＣ系统为５０３％。结论两系统对胰腺癌细胞ＰＣ２均有很好的杀伤和抑制细胞生长作用，ＨＳＶＴＫ／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.
出处
《中华病理学杂志》
CAS
CSCD
北大核心
1998年第6期412-415,共4页
Chinese Journal of Pathology
关键词
胰腺肿瘤
PC-2细胞
HSV-TK
GCV
CD
5-FC
Pancreatic neoplasms Gene transfer Thymidine kinase Tumor cells, cultured Nucleotide deaminase
