Abstract
Abstract Background: Hepatocellular carcinoma (HCC) is the third most important cause of cancer death worldwide. Sorafenib, a multikinase inhibitor improved outcomes in patients with hepatocellular carcinoma (HCC) by inhibiting angiogenesis. Epigenetic research suggests that many cancers may not be caused by mutations in genes but by chemical modifications that change how the genes function. DNA methylation and histone deacetylation are two of the more widely studied epigenetic mechanisms. Inhibitors of DNA methylation (Vidaza) and histone deacetylation (SAHA) have shown inhibited cell growth and induced apoptosis in liver cancer cells. We investigated the cytotoxicity of combination of Sorafenib with SAHA or Vidaza in two liver cancer cell lines HepG2 and Hep3B. METHODS: HepG2 and Hep3B cells in log phase growth were treated simultaneously with sorafenib (0.5-10 µM) and/or vidaza (1.25-10 µM) or SAHA (1.25-10 µM) for 72 hours. Following drug treatment, MTS assay was used as the endpoint for cell proliferation and the IC50 values and combination indices (CI) were derived using Calcusyn software (Biosoft, Cambridge, UK). Each combination was repeated at least three times. RESULTS: The mean single agent IC50's for Sorafenib, Vidaza and SAHA were 6.83±0.44 µM, 10.33±2.91µM, and 11.5±4.25 µM, respectively in HepG2 cells and 6.25±0.20 µM, 11.50±0.41 µM, and 4.25±0.20 µM, respectively in Hep3B cells. The combination indices were:CombinationsHepG2Hep3BSorafenib and Vidaza0.72+0.130.73+0.12Sorafenib and SAHA0.77+0.130.68+0.05 CONCLUSIONS: The CI's for both combinations demonstrated synergistic effects in each of the cell lines. The molecular mechanism behind the synergistic effect of sorafenib in combination with vidaza or SAHA in liver cancer in underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5024.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.