Furosemide, a blocker of Na+/K+/2Cl- cotransporter, diminishes proliferation of poorly differentiated human gastric cancer cells by affecting G0/G1 state
Furosemide, a blocker of Na+/K+/2Cl- cotransporter, diminishes proliferation of poorly differentiated human gastric cancer cells by affecting G0/G1 state
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DOI：
10.2170/physiolsci.rp010806
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发表时间：
2006-12-01
影响因子：
2.3
通讯作者：
Marunaka, Yoshinori
中科院分区：
文献类型：
--
作者：
Shiozaki, Atsushi;Miyazaki, Hiroaki;Marunaka, Yoshinori
速尿是Na+/K+/2Cl（-）共转运体（NKCC）阻滞剂，常作为利尿剂用于改善癌症患者的水肿、腹水和胸腔积液。本研究的目的是研究NKCC阻滞剂是否会影响癌细胞的生长。如果是这样，我们将澄清这一行动的机制。我们发现，低分化胃癌细胞（MKN45）表达NKCC1 mRNA的水平是中等分化胃癌细胞（MKN28）的3倍，且MKN45中的NKCC活性高于MKN28。细胞增殖试验表明，速尿显著抑制MKN45细胞的细胞生长，而对MKN28细胞无抑制作用。通过流式细胞术分析，我们发现暴露于速尿使MKN45细胞在G(0)/G(1)期停留的时间更长，而MKN28细胞则没有。基于这些观察结果，我们发现速尿通过延缓NKCC高表达和活性的低分化胃腺癌细胞的G(1)-S期进展来减缓细胞生长，但在低表达和NKCC活性的中等分化胃腺癌细胞中则没有这种作用。
Furosemide, a blocker of Na+/K+/2Cl(-) cotransporter (NKCC), is often used as a diuretic to improve edema, ascites, and pleural effusion of patients with cancers. The aim of the present study was to investigate whether an NKCC blocker affects cancer cell growth. If so, we would clarify the mechanism of this action. We found that poorly differentiated gastric adenocarcinoma cells (MKN45) expressed the mRNA of NKCC1 three times higher than moderately differentiated ones (MKN28) and that the NKCC in MKN45 showed higher activity than that in MKN28. A cell proliferation assay indicates that furosemide significantly inhibited cell growth in MKN45 cells, but not in MKN28 cells. Using flow cytometrical analysis, we found that the exposure to furosemide brought MKN45 cells to spend more time at the G(0)/G(1) phase, but not MKN28 cells. Based on these observations, we indicate that furosemide diminishes cell growth by delaying the G(1)-S phase progression in poorly differentiated gastric adenocarcinoma cells, which show high expression and activity of NKCC, but not in moderately differentiated gastric adenocarcinoma cells with low expression and NKCC activity.