Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness

被引：153

作者：

Duxbury, MS ^{[1
]}

Waseem, T ^{[1
]}

Ito, H ^{[1
]}

Robinson, MK ^{[1
]}

Zinner, MJ ^{[1
]}

Ashley, SW ^{[1
]}

Whang, EE ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 309卷 / 02期

关键词：

ghrelin; cachexia; Akt; pancreatic adenocarcinoma; cancer; GHS-R; PANC1; MIAPaCa2; BxPc3; Capan2; invasion;

D O I：

10.1016/j.bbrc.2003.08.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：464 / 468

页数：5

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