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心房利钠肽和长效利钠肽抑制人前列腺癌细胞中MEK 1/2的激活。

Atrial natriuretic peptide and long acting natriuretic peptide inhibit MEK 1/2 activation in human 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, FL 33612, USA.

出版信息

Anticancer Res. 2007 Nov-Dec;27(6B):3813-8.

PMID:18225537
Abstract

BACKGROUND

Atrial natriuretic peptide and long acting natriuretic peptide have anticancer effects in human prostate adenocarcinomas.

MATERIALS AND METHODS

Atrial natriuretic peptide, long acting natriuretic peptide and cyclic GMP's effects on MEK 1/2 kinase were examined in human prostate adenocarcinoma cells.

RESULTS

Atrial natriuretic peptide and long acting natriuretic peptide decreased the activation of MEK 1/2 over a concentration range of 0.01 microM to 10 microM. Long acting natriuretic peptide and atrial natriuretic peptide (each 10 microM) inhibited the phosphorylation of MEK 1/2 kinase 97% (p < 0.00001) and 88% (p < 0.00001), respectively. The inhibition of MEK 1/2 was maximal at two hours, and ceased by four hours, secondary to both peptides. The ability of peptides to inhibit MEK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited MEK 1/2 phosphorylation by 93%.

CONCLUSION

Atrial natriuretic peptide and long acting natriuretic peptide both inhibit MEK 1/2 kinase mediated via cyclic GMP as part of their anticancer mechanism(s) of action.

摘要

背景

心房利钠肽和长效利钠肽在人类前列腺腺癌中具有抗癌作用。

材料与方法

在人类前列腺腺癌细胞中检测心房利钠肽、长效利钠肽和环磷酸鸟苷对MEK 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,心房利钠肽和长效利钠肽降低了MEK 1/2的激活。长效利钠肽和心房利钠肽(各10微摩尔)分别抑制MEK 1/2激酶磷酸化97%(p < 0.00001)和88%(p < 0.00001)。两种肽对MEK 1/2的抑制在两小时时达到最大,四小时时停止。肽抑制MEK 1/2的能力被环磷酸鸟苷抗体抑制,且环磷酸鸟苷本身将MEK 1/2磷酸化抑制了93%。

结论

心房利钠肽和长效利钠肽均通过环磷酸鸟苷介导抑制MEK 1/2激酶,这是它们抗癌作用机制的一部分。

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