Open AccessColon cancer cells with high invasive potential are susceptible to induction of apoptosis by a selective COX‐2 inhibitor
Author(s) -
Chen WeiShone,
Liu JinHwang,
Wei SungJen,
Liu Jacqueline Ming,
Hong ChiYuan,
Yang Wen K.
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01429.x
Subject(s) - etodolac , tunel assay , apoptosis , dna fragmentation , colorectal cancer , in vivo , growth inhibition , in vitro , terminal deoxynucleotidyl transferase , cancer research , biology , cancer , microbiology and biotechnology , programmed cell death , medicine , pharmacology , biochemistry
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/lnv1, HT‐29/ Inv2 and HT‐29/lnv3, 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 LD 50 being 0.5 m M for highly invasive HT‐29/lnv2 and HT‐29/lnv3 cells, 0.6 m M for slightly less invasive HT‐29/lnv1, and 1.8 m M for the parental HT‐29. Treatment of the highly invasive HT‐29/lnv2 and Inv3 variants with as little as 0.1 m M 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/lnv3 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. (Cancer Sci 2003; 94: 253–258)