IDENTIFICATION OF GASTRIN AS A GROWTH PEPTIDE IN HUMAN PANCREATIC-CANCER
IDENTIFICATION OF GASTRIN AS A GROWTH PEPTIDE IN HUMAN PANCREATIC-CANCER
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DOI：
10.1152/ajpregu.1995.268.1.r135
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发表时间：
1995-01-01
影响因子：
2.8
通讯作者：
ZAGON, IS
中科院分区：
文献类型：
--
作者：
SMITH, JP;FANTASKEY, AP;ZAGON, IS
本研究报告的第一个证据表明，胃肠道肽胃泌素刺激几个人胰腺癌细胞在培养和移植到裸鼠的肿瘤的生长。在与结合亲和力相当的剂量下，胃泌素促进了所有测试细胞系的生长，为生理学相关受体提供了证据。胃泌素的刺激作用被CCK-B/胃泌素受体拮抗剂L-365，260阻断，而不被CCK-A受体拮抗剂L-364，718阻断。L-365，260可抑制培养的PANC-1细胞的生长，表明PANC-1细胞紧张性地产生胃泌素以调节生长。用1%牛血清白蛋白（稀释剂）、五肽胃泌素（1 mg/kg）或L-365，260（1 mg/kg）每日两次皮下处理携带PANC-1异种移植物的无胸腺裸鼠24天。发现五肽胃泌素处理小鼠的肿瘤比对照组更重，蛋白质和DNA含量更高，而L-365，260处理小鼠的肿瘤中这些值都降低了。用肽或拮抗剂处理的动物的肿瘤中受体结合能力改变，表明调节过程。在移植的PANC-1人肿瘤中检测到胃泌素免疫反应性。这些结果将胃泌素鉴定为有效的营养肽，其积极刺激人胰腺癌的生长，并且通过CCK-B/胃泌素样受体这样做。
The present study reports the first evidence that the gastrointestinal peptide gastrin stimulates the growth of several human pancreatic cancer cells in culture and in tumors transplanted to nude mice. Gastrin promoted growth of all cell lines tested at a dose comparable to the binding affinity, providing evidence for a physiologically relevant receptor. The stimulatory effects of gastrin were blocked by the CCK-B/gastrin receptor antagonist L-365,260 and not by the CCK-A receptor antagonist L-364,718. Growth of PANC-1 cells in culture were inhibited by L-365,260, suggesting that gastrin is tonically produced by PANC-1 cells for regulation of growth. Athymic nude mice bearing PANC-1 xenografts were treated for 24 days subcutaneously with either 1% bovine serum albumin (diluent), pentagastrin (1 mg/kg), or L-365,260 (1 mg/kg) twice daily. Tumors from the pentagastrin-treated mice were found to weigh more and have greater protein and DNA content than controls, whereas these values were all decreased in tumors of L-365,260-treated mice. Receptor binding capacity changed in tumors of animals treated with the peptide or antagonist, suggesting a regulatory process. Gastrin immunoreactivity was detected in a transplanted PANC-1 human tumor. These results identify gastrin as a potent trophic peptide that actively stimulates growth of human pancreatic cancer and does so through a CCK-B/gastrin-like receptor.