Hoosein N M, Black B E, Brattain D E, Brattain M G
Bristol-Baylor Laboratory, Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Regul Pept. 1989 Jan;24(1):15-26. doi: 10.1016/0167-0115(89)90207-3.
The effects of vasoactive intestinal polypeptide (VIP) and dibutyryl cyclic adenosine 3':5'monophosphate (dbcAMP) on two human colon carcinoma cell lines, HCT 116 and GEO, were investigated. VIP and dbcAMP inhibited the growth of both cell lines in monolayer culture in a dose-dependent manner. Within 6 h of treatment with 1 mM dbcAMP or 0.3 microM VIP, numerous mucin-like droplets were secreted by GEO cells. VIP and dbcAMP also increased carcinoembryonic antigen (CEA) secretion. In both cell lines, a 9-fold increase in conditioned medium CEA levels was observed at 1 mM dbcAMP and a 2.6-fold increase at 1.5 microM VIP. Time- and concentration-dependent evaluation in cAMP levels were elicited by VIP in the two cell lines. Immunocytochemical studies for cell-surface glycoprotein detection in GEO cells showed that VIP induced a morphological and functional organization of mucin-secreting cells. These results indicate that VIP and dbcAMP have antiproliferative and strong differentiation-promoting effects in colon cancer cells. This is the first report of VIP-induced mucin secretion in colon tumor cells.
研究了血管活性肠肽（VIP）和二丁酰环磷腺苷（dbcAMP）对两种人结肠癌细胞系HCT 116和GEO的影响。VIP和dbcAMP在单层培养中以剂量依赖性方式抑制两种细胞系的生长。在用1 mM dbcAMP或0.3 μM VIP处理6小时内，GEO细胞分泌了大量粘蛋白样小滴。VIP和dbcAMP还增加了癌胚抗原（CEA）的分泌。在两种细胞系中，在1 mM dbcAMP时条件培养基CEA水平增加了9倍，在1.5 μM VIP时增加了2.6倍。VIP在两种细胞系中引起了cAMP水平的时间和浓度依赖性变化。对GEO细胞中细胞表面糖蛋白检测的免疫细胞化学研究表明，VIP诱导了粘蛋白分泌细胞的形态和功能组织。这些结果表明，VIP和dbcAMP在结肠癌细胞中具有抗增殖和强烈的促分化作用。这是关于VIP诱导结肠肿瘤细胞分泌粘蛋白的首次报道。
