ABSTRACT
Background and purpose:Previous studies have suggested Na+-Ca2+ exchanger isoform 1 (NCX1) as a key component of calcium homeostasis was involved in the tumorigenesis. However, the role of NCX1 and calcium signal in tumorigenesis of hepatocellular carcinoma (HCC) has not been explored. This study aimed to investigate the effect of NCX1 on cell proliferation and migration of HCC HepG2 cells in vitro and the possible mechanism.Methods:Both the real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were applied to assess the expression of NCX1 mRNA and protein in normal hepatic cells (LO2), HCC cell line (HepG2), human normal hepatic tissues and hepatocellular carcinoma tissues. The change of intracellular calcium signal in LO2 and HepG2 cells via acti-vated NCX1 channel in the presence or absence of Na+ was examined by a confocal laser scanning microscope. The effects of NCX1 special inhibitor KB-R7943 on cell proliferation and migration of HepG2 cells were measured by MTT and cellscratch test.Results:Both mRNA and protein expression of NCX1 were higher in HCC tissues and cell line HepG2 than in the normal tissues and cell line LO2 (P<0.05). The activation of NCX1 channel induced a slight rise in cytoplasmic Ca2+concentration ([Ca2+]cyt) in normal cells, but caused a marked increase in cancer cells. And the NCX1 activation induced intracellular calcium increase was significantly reversed by NCX1 inhibitor KB-R7943 (P<0.05). Both NCX1-mediated proliferation and migration of HepG2 were also significantly attenuated by the KB-R7943 (P<0.05).Conclusion:NCX1 is up-regulated in HCC cells and tissues. The activation of NCX1 mediates intracellular calcium homeostasis. The inhibition of NCX1 activity can suppress the proliferation and migration of HepG2 cells. It is suggested that NCX1 may be involved in the development and progression of HCC.
ABSTRACT
Aim This study aimed at investigating the postconditioning protective effect of KB-R7943 and the proper administration time on cardiac ischemia-reperfusion injury in isolated rat heart. Methods Rat heart was isolated quickly when the animal was anesthetized. With Langendorff perfusion, the left anterior descending coronary artery was ligated for 30 min, then released for 120 min in isolated rat heart. Left ventricular function (LVF) and the infarct size of left ventricle were determined. Result Compared with control, KB-R7943 at 1 ?mol?L-1 perfused during the early period of the reperfusion prevented the post-ischemic depression of LVF, decreased the infarct size by 77 %(P