ESTABLISHMENT AND IN-VIVO CHARACTERIZATION OF MULTIDRUG-RESISTANT DUNNING R3327 RAT PROSTATE-CARCINOMA CELL-LINES

被引:18
作者
BASHIR, I
SIKORA, K
ABEL, P
FOSTER, CS
机构
[1] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT CLIN ONCOL,LONDON W12 0NN,ENGLAND
[2] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT SURG,LONDON W12 0NN,ENGLAND
[3] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT HISTOPATHOL,LONDON W12 0NN,ENGLAND
关键词
D O I
10.1002/ijc.2910570519
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We describe the selection of 3 new multidrug-resistant cell lines derived from tumor cells of different metastatic phenotypes within the Dunning R3327 model of rat prostatic carcinoma. Cell lines of weak (AT2) and strong (AT3 and MAT-LyLu) metastatic behaviour were culture in vitro and challenged with doxorubicin at progressively increasing concentrations. Chemosensitivity was determined colorimetrically by release of precipitated formazan pigment (MTT assay). Expression of the multidrug-resistance glycoprotein (P-170) was monitored immunocytochemically and by Western blottig using monoclonal antibody C219. The behaviour of the parental and resultant drug-resistant cells was assessed by their growth in syngeneic rats. Doxorubicin challenge of the initially drug-sensitive parental prostatic carcinoma cell lines resulted in the rapid development of multidrug resistance together with simultaneous expression of P-glycoprotein. While lung and lymph-node metastases developed in host animals inoculated with parental AT3 and MAT-LyLu cells, no metastases developed in the multidrug-resistant progeny of these cell lines. This study has shown that Dunning rat prostate-carcinoma cell lines, previously sensitive to different cytotoxic agents, rapidly become multidrug-resistant and express P-glycoprotein following exposure to doxorubicin. Furthermore, development of multidrug resistance is associated with a less aggressive tumor phenotype and loss of metastatic potential. Nevertheless, it is unlikely that the non-metastatic phenotype of Dunning rat prostatic carcinoma cells is solely associated with expression of P-glycoprotein. These new multidrug-resistant cell lines exhibiting an altered behavioral phenotype will provide a valuabhle model with which to analyze the relationship between expression of P-glycoprotein and the metastatic phenotype of prostatic carcinoma cells. (C) 1994 Wiley-Liss, Inc.
引用
收藏
页码:719 / 726
页数:8
相关论文
共 29 条
[1]   DIFFERENCES IN EXPRESSION OF OLIGOSACCHARIDE DETERMINANTS BY PHENOTYPICALLY DISTINCT SUBLINES OF THE DUNNING 3327 RAT PROSTATE-CANCER [J].
ABEL, PD ;
FOSTER, CS ;
TEBBUTT, S ;
WILLIAMS, G .
JOURNAL OF UROLOGY, 1990, 144 (03) :760-765
[2]   CELL-SURFACE OLIGOSACCHARIDES EXPRESSED BY PHENOTYPICALLY DISTINCT SUBLINES OF THE DUNNING-3327 RAT PROSTATE-CANCER [J].
BASHIR, I ;
SIKORA, K ;
FOSTER, CS .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1990, 18 (05) :968-969
[3]  
BATIST G, 1986, J BIOL CHEM, V261, P5544
[4]  
BECK WT, 1986, CANCER RES, V46, P4571
[5]   OVER-EXPRESSION OF MDR1 GENE WITH NO DNA AMPLIFICATION IN A MULTIPLE-DRUG-RESISTANT HUMAN OVARIAN-CARCINOMA CELL-LINE [J].
BENARD, J ;
DASILVA, J ;
TEYSSIER, JR ;
RIOU, G .
INTERNATIONAL JOURNAL OF CANCER, 1989, 43 (03) :471-477
[6]  
BHALLA K, 1985, CANCER RES, V45, P3657
[7]  
BIEDLER JL, 1992, CANCER-AM CANCER SOC, V70, P1799, DOI 10.1002/1097-0142(19920915)70:4+<1799::AID-CNCR2820701623>3.0.CO
[8]  
2-B
[9]   MEMBRANE-MEDIATED DRUG-RESISTANCE AND PHENOTYPIC REVERSION TO NORMAL GROWTH-BEHAVIOR OF CHINESE-HAMSTER CELLS [J].
BIEDLER, JL ;
RIEHM, H ;
PETERSON, RHF ;
SPENGLER, BA .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1975, 55 (03) :671-680
[10]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3