心房利钠肽和长效利钠肽抑制前列腺癌细胞中的ERK 1/2。

Atrial natriuretic peptide and long acting natriuretic peptide inhibit ERK 1/2 in prostate cancer cells.

作者信息

Sun Ying, Eichelbaum Ehrentraud J, Wang Hai, Vesely David L

机构信息

Department of Internal Medicine, University of South Florida Cardiac Hormone Center and James A. Haley Veterans Medical Center Tampa, Florida 33612, USA.

出版信息

Anticancer Res. 2006 Nov-Dec;26(6B):4143-8.

PMID:17201125

Abstract

BACKGROUND

Atrial natriuretic peptide (ANP) and long acting natriuretic peptide (LANP) have anticancer effects in human prostate adenocarcinomas.

MATERIALS AND METHODS

ANP, LANP and cyclic GMP's effects on extracellular signal-regulated kinase (ERK) 1/2 kinase were examined in human prostate adenocarcinoma cells.

RESULTS

ANP and LANP decreased the activation of ERK 1/2 over a concentration range of 0.01 microM to 10 microM. ANP and LANP's maximal inhibition of the phosphorylation of ERK 1/2 kinase were 94% and 88% (p < 0.0001), respectively. ANP had significant effects within five min at its 10 microM concentration. The inhibition of ERK 1/2 lasted for at least two h, where it was maximal, secondary to both peptides. Their ability to inhibit ERK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited ERK 1/2 phosphorylation.

CONCLUSION

ANP and LANP both inhibit ERK 1/2 kinase mediated via cyclic GMP as part of their anticancer mechanism(s) of action.

摘要

背景

心房利钠肽（ANP）和长效利钠肽（LANP）对人前列腺腺癌具有抗癌作用。

材料与方法

在人前列腺腺癌细胞中检测了ANP、LANP和环磷酸鸟苷（cGMP）对细胞外信号调节激酶（ERK）1/2激酶的影响。

结果

在0.01微摩尔至10微摩尔的浓度范围内，ANP和LANP降低了ERK 1/2的活性。ANP和LANP对ERK 1/2激酶磷酸化的最大抑制率分别为94%和88%（p < 0.0001）。在10微摩尔浓度下，ANP在5分钟内就产生了显著作用。ERK 1/2的抑制作用持续至少2小时，在此期间达到最大抑制，这两种肽均可导致这种抑制。它们抑制ERK 1/2的能力被环磷酸鸟苷抗体所抑制，并且环磷酸鸟苷本身也抑制ERK 1/2的磷酸化。