Selective CCK-A but not CCK-B receptor antagonists inhibit HT-29 cell proliferation: synergism with pharmacological levels of melatonin.

摘要: Some data suggest that cholecystokinin (CCK) receptor agonists stimulate the growth of colon cancer. Melatonin, an endogenous indoleamine with strong antioxidant properties, displays antiproliferative and proapoptotic properties both in vivo or vitro several types tumors. We used HT-29 human cancer cells, expressing CCK receptors, to test effects antagonists CCK-A and/or CCK-B their possible synergism melatonin. cells were cultured RPMI 1640 medium supplemented fetal bovine serum at 37 degrees C. Cell proliferation was assessed by incorporation [3H]-thymidine into DNA. Annexin V-FITC plus propidium iodine for flow cytometry apoptosis/necrosis evaluation. The following drugs tested: gastrin (CCK-B agonist); CCK-8s (CCK-A proglumide antagonist); lorglumide PD 135,158 antagonist weak devazepide L 364,718 365,260 antagonist), results shown a lack on cell proliferation, whereas induced high doses. order effect other > proglumide. These produce death mainly inducing apoptosis. Melatonin showed millimolar concentrations, it apoptotic death. generally enhanced devazepide, increased proglumide-induced melatonin are useful controlling culture combined therapy significantly increases efficiency.