Colon cancer cells with high invasive potential are susceptible to induction of apoptosis by a selective COX-2 inhibitor

被引:18
作者
Chen, WS [1 ]
Liu, JH
Wei, SJ
Liu, JM
Hong, CY
Yang, WK
机构
[1] Vet Gen Hosp, Div Colorectal Surg, Taipei, Taiwan
[2] Vet Gen Hosp, Div Med Oncol, Taipei, Taiwan
[3] Natl Yang Ming Univ, Taipei 112, Taiwan
[4] Natl Hlth Res Inst, Taipei 112, Taiwan
[5] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan
[6] Natl Taiwan Univ Hosp, Sch Dent, Dept Prosthet Dent, Taipei 115, Taiwan
关键词
D O I
10.1111/j.1349-7006.2003.tb01429.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cyclooxygenase-2 (COX-2) expression has been shown to correlate with the invasiveness of colon cancer cells. To further investigate this positive correlation and its possible therapeutic implications, a selective COX-2 inhibitor, etodolac, was tested on three variants of HT-29 colon cancer cell lines, HT-29/Inv1, HT-29/Inv2 and HT-29/Inv3, with graded increases of in vitro Matrigel invasive potential and COX-2 expression levels. HT-29 variants with higher invasive potential were found to be more sensitive to etodolac by in vitro growth inhibition assays, the estimated LD50 being 0.5 mM for highly invasive HT-29/Inv2 and HT-29/Inv3 cells, 0.6 mM for slightly less invasive HT-29/Inv1, and 1.8 mM for the parental HT-29. Treatment of the highly invasive HT-29/Inv2 and Inv3 variants with as little as 0.1 mM etodolac in the growth medium produced signs of apoptosis, as detected by DNA fragmentation and TUNEL (terminal deoxynucleotidyl transferase dUTP-biotin nick end labeling) assay. In vivo experiments in SCID mice showed that etolodac inhibited the growth of subcutaneous tumors induced by HT-29/Inv3 cells significantly more than those by the parental HT-29 cells. These results suggest that COX-2 inhibitors have a potential role in prevention of tumor invasion in colon cancer patients.
引用
收藏
页码:253 / 258
页数:6
相关论文
共 27 条
[1]  
Achiwa H, 1999, CLIN CANCER RES, V5, P1001
[2]  
Chen WS, 2001, INT J CANCER, V91, P894, DOI 10.1002/1097-0215(200102)9999:9999<894::AID-IJC1146>3.0.CO
[3]  
2-#
[4]   Cyclooxygenase, NSAIDs, and colorectal cancer [J].
DuBois, RN ;
Smalley, WE .
JOURNAL OF GASTROENTEROLOGY, 1996, 31 (06) :898-906
[5]  
Elder DJE, 1997, CLIN CANCER RES, V3, P1679
[6]  
Fujita T, 1998, CANCER RES, V58, P4823
[7]   ETODOLAC SELECTIVELY INHIBITS HUMAN PROSTAGLANDIN-G/H-SYNTHASE-2 (PGHS-2) VERSUS HUMAN PGHS-1 [J].
GLASER, K ;
SUNG, ML ;
ONEILL, K ;
BELFAST, M ;
HARTMAN, D ;
CARLSON, R ;
KREFT, A ;
KUBRAK, D ;
HSIAO, CL ;
WEICHMAN, B .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 281 (01) :107-111
[8]   COX-2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX-2 inhibitor celecoxib [J].
Grösch, S ;
Tegeder, I ;
Niederberger, E ;
Bräutigam, L ;
Geisslinger, G .
FASEB JOURNAL, 2001, 15 (12) :2742-+
[9]  
Hara A, 1997, JPN J CANCER RES, V88, P600
[10]  
KUJUBU DA, 1993, J BIOL CHEM, V268, P5425