Background: Endothelin-1 (ET-1) is a potent mitogen involved in tumor cell growth and angiogenesis. The aim of this study is to explore the effect of ET-1 on the proliferation of human lung adenocarcinoma cells SPC-A1.
Methods: Cell number was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide] assay. Cell cycle was detected by flow cytometry.
Results: ET-1 (1×10⁻¹⁵ -1×10⁻⁸ mol/L) enhanced SPC-A1 cell growth in a dose-dependent manner in vitro, with the greatest effect beginning at 1×10⁻¹¹ mol/L. Effect of ET-1 (1×10⁻¹⁰ mol/L) on the proliferation of SPC-A1 cells was completely blocked by BQ123 (1×10⁻⁷ mol/L), a highly selective endothelin receptor A (ETA) antagonist (P < 0.05), not by BQ788 (1×10⁻⁷ mol/L), a highly selective endothelin receptor B (ETB) antagonist. BQ123 could significantly reduce the basal growth of SPC-A1 cells (P < 0.05), but BQ788 had no such effect. Proliferation induced by ET-1 (1×10⁻¹⁰ mol/L) could also be blocked by the addition of either ethylene diamine tetraacetic acid (EDTA, 0.4mmol/L) or nifedipine (1μmol/L). ET-1 had no significant effect on SPC-A1 cell cycle.
Conclusions: ET-1 enhances SPC-A1 cell proliferation by the activation of ETA receptor. Ca(2+) influx from voltage dependent calcium-channel contributes to this process.