Abstract 3540: Reduction in cell viability of hepatoblastoma cells following inhibtion of Hsp90

Background: Hepatoblastoma (HB) is the most frequent liver tumor in children. While most tumors respond well to treatment with good outcomes, there are a subgroup of refractory tumors for which novel therapies are required. Emerging literature has suggested a role of Hsp90 in HB progression. One possible mechanism hypothesizes that Hsp90 helps stabilize misfolded proteins that contribute to HB progression including β-catenin. Our study aimed to investigate if inhibition of Hsp90 would affect the cell viability of hepatoblastoma cell lines in vitro. Methods: Commercially available HEPG2, and patient xenograft-derived hepatoblastoma cell lines (HB214, HB279, and HB303) were analyzed for differences in Hsp90 gene expression by qRTPCR as well as cell viability (n = 3 replicates for each cell line) using the MTS assay. Differences in cell viability for each cell line were further examined after treatment with a 0.1µM or 0.25µM dose of 17-AAG (an HSP90 inhibitor) for 48H. We examined gene expression and the MTS assay cell viability data using linear mixed effects modelling followed by t-tests to examine specific comparisons (significance at p < 0.05). Results: Hsp90 gene expression was significantly increased in HEPG2 cells (p < 0.001) and in HB279 cells (p < 0 .05), but not in HB214, or HB303 cells, compared to HUVECs control cells. Examining clinically relevant characteristics, significant improvements to model fit were found with the inclusion of sex (p < 0.01), β-catenin deletion status (p < 0.01), and a higher PRETEXT stage but not from examining if cell lines were derived from metastatic parent tumors. While we observed no significant cell line viability differences between individual HB cell lines at baseline (0µM 17-AAG treatment) or overall significant differences for treatment with either 0.1µM or 0.25µM dosages of 17-AAG, there were differences in cell viability for individual HB cell lines. We observed significant decreases in cell viability in HEPG2 cells with 0.1µM (p < 0.05) and 0.25µM (p < 0.05), as well as in HB279 cells with 0.1µM (p < 0.05) and 0.25µM (p < 0.05) 17-AAG treatments but observed no effect of 17-AAG treatment on cell viability in HB214, or HB303 cells. Similar improvements in model fit were observed with the inclusion of sex (p < 0.01), β-catenin deletion status (p < 0.01), and a higher PRETEXT stage (p < 0.001), but not from examining if cell lines were derived from metastatic parent tumors. Conclusion: HB cell lines express Hsp9