[两种前药敏感性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].

作者信息

Zhang L, Liu T, Cui Q

机构信息

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730.

出版信息

Zhonghua Bing Li Xue Za Zhi. 1998 Dec;27(6):412-5.

PMID:11244949

Abstract

OBJECTIVE

To compare the killing effects of herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system versus cytosine deaminase (CD)/5-fluorocytosine (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 IC50 values (concentration of drug at which cell growth is inhibited by 50%) of the transduced cells were measured by MTT method. The bystander effects in the two systems were also compared.

RESULTS

The IC50 value of HSV-TK-transduced cells to GCV was (1.06 +/- 0.12) micromol/L and 558-fold lower than parental PC-2 cells, while the IC50 value of CD-transduced cells to 5-FC.00 was (33.00 + 0.95) micromol/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 effective 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.

摘要

目的

比较单纯疱疹病毒胸苷激酶（HSV-TK）/更昔洛韦（GCV）系统与胞嘧啶脱氨酶（CD）/5-氟胞嘧啶（5-FC）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，并转导至胰腺癌细胞系。采用MTT法测定转导细胞对前体药物的敏感性及半数抑制浓度（IC50值，即抑制细胞生长50%时的药物浓度）。同时比较两种系统的旁观者效应。

结果

转导HSV-TK的细胞对GCV的IC50值为（1.06±0.12）μmol/L，比亲代PC-2细胞低558倍；转导CD的细胞对5-FC的IC50值为（33.00±0.95）μmol/L，比亲代PC-2细胞低258倍。含10%转导细胞的混合细胞在TK/GCV和CD/5-FC系统中分别表现出39%和50.3%的生长抑制。