Resistance of colon cancer cells to long-term 5-fluorouracil exposure is correlated to the relative level of Bcl-2 and Bcl-xL in addition to Bax and p53 status

被引:189
作者
Violette, S
Poulain, L
Dussaulx, E
Pepin, D
Faussat, AM
Chambaz, J
Lacorte, JM
Staedel, C
Lesuffleur, T [1 ]
机构
[1] Univ Paris 06, INSERM, U505, Paris, France
[2] CRLCC Francois Baclesse, UPRES EA 1772, Caen, France
[3] Hop Hotel Dieu, EPI 9912, F-75181 Paris, France
关键词
5-FU resistance; p53 and bax status; Bcl-2 and Bcl-x(L) expression; colon cancer cells;
D O I
10.1002/ijc.10146
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Defects in apoptosis have been implicated in chemoresistance of colon cancer cells. We report here the ability to resist to 5-fluorouracil-induced apoptosis of 8 colon cancer cell lines differing in p53 and box status: p53(-/0)bax(+/+) for TC7, SW480, HT-29, pS3(+/+)bax(-/-) for LS174T, LoVo; p53(+/+) bax(+/-) for HCT116; p53(+/+) or p53(+/0)bax(+/+) for LS513 or HCT-EB, respectively. To approximate to the in vivo therapy, the cell lines were exposed to a long-term treatment of 5-FU. The analysis of proteins implicated in the apoptotic pathway has shown that the independent analysis of p53 or box status was not sufficient to predict the extent of drug-resistance of all cell lines. In p53(+/+) cell lines but not in p53(-/0) cell lines, a low level of the pro-apoptotic Bax protein was correlated with a greater resistance of cells to 5-FU. In addition, we found that high levels of anti-apoptotic Bcl-2 and Bcl-x(L) proteins combined with a low level of Bax were correlated to high 5-FU resistance of wild-type p53 cell lines. The same correlation was obtained for 2 out of 3 mutated p53 cell lines. In conclusion, the relative levels of Bcl-2, Bcl-x(L) and Bax may altogether contribute to determine the resistance of a majority of colon tumor cells to long-term 5-FU treatment, whatever their p53 status. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:498 / 504
页数:7
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