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

Wei-Shone Chen, Jin-Hwang Liu, Sung-Jen Wei, Jacqueline Ming Liu, Chi-Yuan Hong, Wen K Yang

Division of Colorectal Surgery, Veterans General Hospital-Taipei and National Yang-Ming University, Taiwan. wschen@vghtpe.gov.tw

Cancer science 2003 Mar

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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 LD(50) 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.

Citation

Wei-Shone Chen, Jin-Hwang Liu, Sung-Jen Wei, Jacqueline Ming Liu, Chi-Yuan Hong, Wen K Yang. Colon cancer cells with high invasive potential are susceptible to induction of apoptosis by a selective COX-2 inhibitor. Cancer science. 2003 Mar;94(3):253-8