CORRELATION BETWEEN THE EFFECTS OF BOMBESIN ANTAGONISTS ON CELL-PROLIFERATION AND INTRACELLULAR CALCIUM-CONCENTRATION IN SWISS 3T3 AND HT-29 CELL-LINES

Bombesin (BN) acts as an autocrine mitogen in various human cancers. S everal pseudononapeptide BN-(6-14) analogs with a reduced peptide bond between positions 13 and 14 have been shown to suppress the mitogenic activity of BN or gastrin-releasing peptide (GRP) when assessed by ra dioreceptor or proliferation assays and may have significant clinical applications, The search for potent and safe BN antagonists requires t he evaluation of a large series of analogs in radioreceptor and prolif eration assays, In this paper, we report that the ability of BN analog s to inhibit BN-induced calcium transients in Swiss 3T3 cells shows a high correlation with their inhibitory potency as evaluated by classic al proliferation tests. The assay of calcium transients allows a rapid characterization of new BN analogs (in terms of minutes rather than d ays) and can be adapted as a labor and cost-effective screening step i n the selection of potentially relevant BN antagonists for further cha racterization in cell proliferation systems. We also observed that res ults from the assay of calcium transients in Swiss 3T3 cells can be co rrelated with the results of the proliferative response in HT-29 cells , a cell line that does not seem to use the same early transmembrane i onic signal system, This result suggests that the calcium pathway is n ot mandatory for triggering cell division by the BN receptor.