Amphotericin B up-regulates angiogenic genes in hepatocellular carcinoma cell lines

Abstract

Background: Amphotericin B (AmB) has a discordant influence on epirubicin (4′-epidoxorubicin) cytotoxicity in hepatocellular carcinoma (HCC). This indicates that the cellular function of HCC may be significantly influenced by AmB. Whether the influence of AmB on HCC has any possibility to influence cancer growth has not been studied. This study was to try and clarify this issue. Materials and methods: Two HCC cell lines including one without augmentation of the epirubicin cytotoxicity by AmB (cell line A; HCC24/KMUH) and one with this effect (cell line B; HCC38/KMUH) were studied by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and whole human genome microarray (experimental group: 2·5 μg mL-1 AmB). Results: Differential expressions of genes induced by AmB in two cell lines had no influence on cell proliferation as determined by MTT assay. Only cell line B showed up-regulation of genes related to oxidative stress, acute phase reaction, cytokine-cytokine receptor interaction and complement and coagulation cascades. Among the chemokine genes up-regulated by AmB, five genes (CCL2, CXCL1, CXCL5, CXCL6, IL8) were angiogenic. Cell line B also showed up-regulation of one angiogenic C10orf10 gene and down-regulation of one angiostatic chemokine gene (CXCL10). Up- or down-regulation of other genes in cell line A and B did not show any evidence to promote angiogenesis. Conclusion: AmB has the capacity to concomitantly up-regulate angiogenic genes in HCC cells susceptible to AmB-induced oxidative stress. © 2009 Stichting European Society for Clinical Investigation Journal Foundation.