Na+/Ca2+ exchanger (NCX) couples the translocation of
Ca2+ to that of Na+ in the opposite direction and contributes to the maintenance of [Ca2+]i homeostasis in a variety of cell types. However, little is known about the role of NCX in the regulation of [Ca2+]i homeostasis in human hepatocellular carcinoma (HCC) cells. Therefore, in the present study, we sought to investigate the expression and functional role of NCX1 in human HCC cells. BTK pathway inhibitor Methods: The expression levels of NCX1 mRNA and protein in human HCC tissues and cells were determined by using real time RT-PCR and western blot. The changes of ([Ca2+]i) were examined by confocal laser scanning microscope. The cell proliferation was examined by using MTT assay. Results: The expression levels of NCX1 mRNA and protein in human HCC tissues were markedly higher than those in normal liver tissues. Likewise, the expression levels of NCX1 mRNA and protein in HepG2 and Bel-7404 cells were also markedly higher than those in LO2 cells. The removal of extracellular Na+ (0Na+) induced the increases of [Ca2+]i in HepG2, Bel-7404, and LO2 cells. But, the increases of [Ca2+]i in both HepG2 and Bel-7404 cells were higher than those in LO2 cells (P < 0.01). The pretreatment of KB-R7943, a NCX1 special antagonist, significantly
inhibited the 0 Na+–induced increase [Ca2+]i in these cell lines. The further experiments showed that KB-R7943 MG-132 cell line inhibited the proliferation of HepG2 and Bel-7404 cells, compared to control. Conclusion: NCX1 is functionally expressed and up-regulated in human HCC cells, regulates [Ca2+]i homeostasis of HCC cells, and mediated the proliferation of HCC cells, which implicates
that NCX1 may play important role in the development and progression of human HCC. Key Word(s): 1. HCC; 2. NCX1; 3. intracellular Ca2+; Presenting Author: PING ZHANG Additional Authors: XIANGYUE CHEN Corresponding Author: XIANGYUE CHEN Affiliations: changzheng hospital Objective: HCC progression is thought to be driven by cancer stem cells (CSCs) through their capacity for self-renewal and production of heterogeneous progeny. The cancer stem cells (CSCs) in hepatocarcinoma have profound implications for cancer treatment. In our study, we evaluated sophocarpine, a compound derived from the foxtail-like sophora herb, for its efficacy to inhibit liver CSCs and its potential mechanism. Methods: CCK8 and cell sphere formation assays were used to evaluate the effect of sophocarpine on liver CSCs in vitro. A subcutaneous xenograft model and a transplanted liver tumor model were used to determine if sophocarpine could target liver CSCs in vivo. Results: Our results showed that sophocarpine could reduce cell viability by inducing cell cycle arrest and the differerntiation of hepatoma cells into hepatocytes.