944. Inhibiting Survivin Expression Enhances Trail-Induced Apoptosis in Human Hepatocellular Carcinoma

Abstract

Background: The fact that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces profound apoptosis in a wide range of tumor cell lines but lacks cytotoxicity to mosnormal cells raises hope that TRAIL might become a novel potential anticancer agent. Our previous studies shown that hepatoma cells are not sensitive to TRAIL treatment . Overexpression of survivin reduced sensitivity of hepatoma cells to TRAIL.The aim of this study is to investigate whether tumor cells escape TRAIL-killing through survivin experssion and how to reverse this resistance. Methods: Human hepatoma cell lines (HepG2, SMMC 7721), cholangiocarcinoma cell line QBC939, no-small-cell lung cancer cell line A549, colorectal adenocarcinoma cell lines (SW480 and HCT-15), and malignant hematopoietic cell line Jurkat, were treated with or without TRAIL protein and survivin antisense oligodeoxynucleotide (ODN) in culture. Survivin mRNA levels in treated cells were detected by semiquantitative RT-PCR. Synchronization of hepatoma cells was used to test the sensitivity of hepatoma cells to TRAIL. Apoptosis and cell cycle were examined by flow cytometry. Cell viability and proliferation assay were evaluated by MTT. In vivo effects of TRAIL plasmid and /or survivin antisense ODN on tumor growth were investigated in a nude mouse HCC model of HepG2 cell grafts in the liver. Results: Survivin mRNA levels varied in cell lines evaluated and negatively correlated to TRAIL-induced apoptosis (r=|[minus]|0.856,p<0.05).