Department of Medicine, USF Cardiac Hormone Center, James A. Haley VA Medical Center and University of South Florida, 13000 Bruce B. Downs Blvd, Tampa, FL 33612, USA.
Mol Cell Biochem. 2012 Dec;371(1-2):209-15. doi: 10.1007/s11010-012-1437-1. Epub 2012 Sep 11.
Signal transducers and activators of transcription (STATs) are the final "switches" that activate gene expression patterns that lead to human malignancy. Extracellular signal-regulated kinases (ERK 1/2) activate STAT 3; four cardiovascular hormones inhibit ERK 1/2 kinases, leading to the hypothesis that they may also inhibit STATs. These four cardiac hormones, i.e., vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP), eliminate human cancers growing in mice. These four cardiac hormones' effects on STATs 1 and 3 were examined in human small-cell lung cancer and human pancreatic adenocarcinoma cells. Vessel dilator, LANP, kaliuretic peptide, and ANP maximally decreased STAT 3 by 88, 54, 55, and 65 %, respectively, at their 1 μM concentrations in human small-cell lung cancer cells and STAT 3 by 66, 57, 70, and 77 % in human pancreatic adenocarcinoma cells, respectively. The cardiac hormones (except LANP) also significantly decreased STAT 3 measured by Western blots. These cardiac hormones did not decrease STAT 1 in either human small-cell lung cancer or pancreatic adenocarcinoma cells. We conclude that these four cardiac hormones are significant inhibitors of STAT 3, but not STAT 1, in human small-cell lung cancer and pancreatic adenocarcinoma cells, which suggests a specificity for these hormones' anticancer mechanism(s) of action enzymology in human cancer cells.
信号转导子和转录激活子（STATs）是激活导致人类恶性肿瘤的基因表达模式的最终“开关”。细胞外信号调节激酶（ERK1/2）激活 STAT3；四种心血管激素抑制 ERK1/2 激酶，这导致了它们可能也抑制 STATs 的假说。这四种心脏激素，即血管扩张剂、长效利钠肽（LANP）、利钾肽和心房利钠肽（ANP），可消除在小鼠中生长的人类癌症。在人类小细胞肺癌和人类胰腺腺癌细胞中，检查了这四种心脏激素对 STATs1 和 3 的影响。血管扩张剂、LANP、利钾肽和 ANP 分别以 1 μM 浓度在人类小细胞肺癌细胞中使 STAT3 最大降低 88%、54%、55%和 65%，在人类胰腺腺癌细胞中使 STAT3 降低 66%、57%、70%和 77%。心脏激素（LANP 除外）也显著降低了 Western blot 测定的 STAT3。这些心脏激素在人类小细胞肺癌或胰腺腺癌细胞中均未降低 STAT1。我们得出结论，这些四种心脏激素是人类小细胞肺癌和胰腺腺癌细胞中 STAT3 的重要抑制剂，但不是 STAT1，这表明这些激素在人类癌细胞中的抗癌作用机制具有特异性。
