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五种心脏激素可减少人类小细胞肺癌细胞的数量。

Five cardiac hormones decrease the number of human small-cell lung cancer cells.

作者信息

Vesely B A, Song S, Sanchez-Ramos J, Fitz S R, Alli A A, Solivan S M, Gower W R, Vesely D L

机构信息

Department of Internal Medicine, University of South Florida Cardiac Hormone Center, Tampa, FL, USA.

出版信息

Eur J Clin Invest. 2005 Jun;35(6):388-98. doi: 10.1111/j.1365-2362.2005.01501.x.

Abstract

BACKGROUND

Four peptide hormones of a family of six hormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-natriuretic peptide (CNP), long acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide, significantly decrease the number of adenocarcinoma cells in culture. The present investigation was designed to determine whether these peptide hormones' effects are specific to adenocarcinomas or whether they might decrease the number of cancer cells of a different type of cancer, i.e. small-cell lung cancer.

METHODS AND MATERIALS

These six hormones were evaluated for their ability to decrease the number and/or proliferation of human small-cell lung cancer cells in culture for 24, 48, 72, and 96 h.

RESULTS

Within 24 h, vessel dilator, LANP, kaliuretic peptide, ANP and their intracellular mediator cyclic GMP, each at 1 microM, decreased the number of small-cell lung cancer cells by 63% (P < 0.001), 21% (P < 0.05), 30% (P < 0.05), 39% (P < 0.05), and 31% (P < 0.05), respectively. There was no proliferation in the 3 days following this decrease in cell number. These same hormones decreased DNA synthesis 68% to 82% (P < 0.001). Brain natriuretic peptide and CNP did not decrease the number of small-cell lung cancer cells or inhibit their DNA synthesis at 1 microM or 10 microM concentrations. Dose-response curves revealed that at 100 microM, the vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect, but CNP caused a 39% decrease. Western blots revealed that the natriuretic peptide receptors A- and C- were present in these cancer cells.

CONCLUSIONS

Five peptide hormones significantly decrease the number of human small-cell lung cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis mediated in part by cyclic GMP.

摘要

背景

一个由六种激素组成的家族中的四种肽类激素,即心房利钠肽(ANP)、脑利钠肽(BNP)、C型利钠肽(CNP)、长效利钠肽(LANP)、血管舒张肽和利钾尿肽,可显著减少培养的腺癌细胞数量。本研究旨在确定这些肽类激素的作用是否对腺癌具有特异性,或者它们是否可能减少不同类型癌症(即小细胞肺癌)的癌细胞数量。

方法和材料

评估这六种激素在培养24、48、72和96小时内减少人小细胞肺癌细胞数量和/或增殖的能力。

结果

在24小时内,血管舒张肽、LANP、利钾尿肽、ANP及其细胞内介质环磷酸鸟苷(cGMP),各自在1微摩尔浓度时,分别使小细胞肺癌细胞数量减少63%(P < 0.001)、21%(P < 0.05)、30%(P < 0.05)、39%(P < 0.05)和31%(P < 0.05)。在细胞数量减少后的3天内没有增殖现象。这些相同的激素使DNA合成减少68%至82%(P < 0.001)。脑利钠肽和CNP在1微摩尔或10微摩尔浓度时,并未减少小细胞肺癌细胞数量或抑制其DNA合成。剂量反应曲线显示,在100微摩尔时,血管舒张肽在24小时内使92%的癌细胞减少,而BNP无作用,但CNP使癌细胞减少39%。蛋白质免疫印迹法显示,利钠肽受体A和C存在于这些癌细胞中。

结论

五种肽类激素在24小时内可显著减少人小细胞肺癌细胞数量,并至少在96小时内抑制其增殖。它们这样做的机制部分涉及通过环磷酸鸟苷介导抑制DNA合成。

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