BACKGROUND The vasoactive peptide endothelin 1 (ET-1) acts via two receptors, endothelin receptors A (ET_A) and B (ET_B). ET-1 is overexpressed by human cancers in vivo and in vitro and may be mitogenic for cancer cells.

RESULTS ET-1 was produced by LIM1215 and HT29 cells (21.3 and 41.7 fmol/ml/10⁶ cells (24 hours); 22.6 and 71.7 fmol/ml/10⁶ cells (48 hours), respectively). ET_A and ET_B receptors were expressed by both cell lines. Addition of ET-1 resulted in a dose dependent increase in cell numbers which was significant at 10⁻⁸–10⁻⁹ M for LIM1215, with the greatest increase at 10⁻⁸ M (32.7% and 28.4% increase above controls at 48 hours and 72 hours; p<0.05) and at 10⁻⁸–10⁻⁹ M for HT29, with the greatest increase at 10⁻⁹ M (13.4% and 15.7% increase above controls at 48 hours and 72 hours; p<0.05). ET_Aantagonists BQ123 and BQ610, but not the ET_B antagonist BQ788, inhibited ET-1 induced proliferation of both LIM1215 and HT29 (p<0.05).

CONCLUSION ET-1 can stimulate the proliferation of colorectal cancer cell lines via the ET_A, but not the ET_B, receptor.