Furosemide, a Blocker of Na+/K+/2Cl− Cotransporter, Diminishes Proliferation of Poorly Differentiated Human Gastric Cancer Cells by Affecting G0/G1 State

The Journal of Physiological Sciences

Yuji Ueda²  Yoshinobu Iwasaki⁵  Atsushi Shiozaki³  Yoshinori Marunaka³  Hiroaki Miyazaki³  Takashi Nakahari⁴  Hirosumi Itoi¹  Naomi Niisato³  Hisakazu Yamagishi² 

[1] Department of Surgery, Graduate School of Acupuncture and Moxibustion, Meiji University of Oriental Medicine;Department of Surgery, Division of Digestive Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine;Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine;Department of Physiology, Osaka Medical College;Department of Respiratory Molecular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine

关键词: gastric cancer cell;    Na+/K+/2Cl− cotransporter (NKCC);    furosemide;    cell cycle;    cell proliferation;   

DOI  :  10.2170/physiolsci.RP010806

学科分类：生理学

来源: Springer

【 摘 要 】

References(31)Cited-By(13)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 G0/G1 phase, but not MKN28 cells. Based on these observations, we indicate that furosemide diminishes cell growth by delaying the G1-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.

【 授权许可】

Unknown