Hepatoma-derived growth factor as a survival factor in human cancer cells. Free

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Hepatoma-derived growth factor (HDGF) is a growth factor originally isolated from a hepatoma cell line and is subsequently found to be overexpressed in a number of human cancer cells. HDGF is known to be mitogenic for a variety of cells, including fibroblasts, vascular smooth muscle cells and endothelial cells. However, whether HDGF is essential for the survival of cancer cells is not yet known. The aim of the present study is to examine the effect of HDGF knock-down on the survival of human cancer cells. By MTT assay, up-regulation of HDGF by transfection with vector carrying HDGF cDNA was found to have a slight growth stimulation effect while down-regulation of HDGF by HDGF specific antisense oligonucleotides suppressed the growth of human hepatocellular carcinoma HepG2 cells. Moreover, by both DNA fragmentation assay and annexin V binding assay, apoptosis was detected in HepG2 cells upon knock-down of HDGF by antisense oligonucleotides. Similar results were obtained in human squamous cell carcinoma A431 cells and other human hepatocellular carcinoma cells, including doxorubicin resistant R-HepG2 cells and Hep3B cells. By the use of Western blot analysis, activation of caspase-3, -8 and -9 was detected in HepG2 cells upon HDGF knock-down by antisense oligonucleotides. The results from the present study suggested that HDGF may be essential for the survival of cancer cells. Knock-down of HDGF will lead to apoptosis in human cancer cells through the activation of caspase-dependent apoptotic pathway.