Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness
Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness
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DOI：
10.1016/j.bbrc.2003.08.024
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发表时间：
2003-09-19
影响因子：
3.1
通讯作者：
Whang, EE
中科院分区：
文献类型：
--
作者：
Duxbury, MS;Waseem, T;Whang, EE
胃饥饿素是一种新发现的强效产氧肽，可能对恶病质患者具有治疗潜力。我们评估了通常与显著恶病质相关的胰腺腺癌是否是一种生长素反应性恶性肿瘤。胰腺腺癌细胞暴露于饥饿素（0-100 nM）。MTT法检测细胞增殖。观察Ghrelin、Ghrelin 1a和1b受体表达及Akt磷酸化情况。通过Matrigel Boyden室法定量胃饥饿素（其拮抗剂D-Lys-GHRP6或P13-K抑制剂Wortmannin）对细胞运动和侵袭性的影响。所有细胞系均表达ghrelin la和1b受体转录物和蛋白，但只有PANC1弱表达ghrelin转录物。10纳摩尔胃饥饿素增加了所有细胞系的增殖、运动性、侵袭性和Akt磷酸化。增殖受剂量依赖性影响，在较高的胃饥饿素浓度下被抑制。D-Lys-GHRP6抑制胃饥饿素诱导的增殖、侵袭和Akt磷酸化。Wortmannin消除了ghrelin对运动性和侵袭性的影响。胰腺腺癌是一种胃促生长素反应性恶性肿瘤。(C) 2003 Elsevier Inc.版权所有。
Ghrelin, a newly described potent orexigenic peptide, may have therapeutic potential in patients with cachexia. We assessed whether pancreatic adenocarcinoma, commonly associated with marked cachexia, is a ghrelin-responsive malignancy. Pancreatic adenocarcinoma cells were exposed to ghrelin (0-100 nM). Proliferation was determined by MTT assay. Ghrelin, ghrelin 1 a and 1b receptor expression and Akt phosphorylation were assessed. The effects of ghrelin (its antagonist D-Lys-GHRP6, or the P13-K inhibitor Wortmannin) on cellular motility and invasiveness were quantified by Matrigel Boyden chamber assay. All cell lines expressed ghrelin la and 1b receptor transcript and protein, but only PANC1 weakly expressed ghrelin transcript. Ten nanomolar ghrelin increased proliferation, motility, invasiveness, and Akt phosphorylation in all cell lines. Proliferation was affected dose-dependently, being suppressed at higher ghrelin concentrations. D-Lys-GHRP6 suppressed ghrelin-induced proliferation, invasion, and Akt phosphorylation. Wortmannin abolished the effects of ghrelin on motility and invasiveness. Pancreatic adenocarcinoma is a ghrelin-responsive malignancy. (C) 2003 Elsevier Inc. All rights reserved.