Der physiologische Östrogenmetabolit 2-Methoxyestradiol induziert tumorspezifische Apoptose bei Zellen humaner hepatozellulärer Karzinome und führt zu Tumorhemmung in vivo

Abstract

Surgery remains the only treatment option with a potential cure for hepatocellular carcinoma. Thus, novel treatment options need to be investigated. 2-Methoxyestradiol (2-ME), a physiological metabolite of estrogen, has been shown to induce apoptosis and to reduce tumor growth in various different tumors. We examined the efficiency of 2-ME in tumor growth inhibition in human hepatoma cell lines. Proliferation assays, staining for apoptosis, and FACS analysis were performed. A subcutaneous tumor model in nude mice was used to assess the in vivo efficacy of 2-ME. We found a growth inhibition from 90% to 98% in all cells after treatment with 2 μM 2-ME for 5 days. Growth inhibition appeared to be caused by induction of apoptosis as shown by specific staining in all cell lines after 2 days of treatment. In contrast, no induetion of apoptosis was seen in normal hepatocytes. 2-ME treated mice showed a 45% lower average tumor volume when compared to non treated control mice. Three out of 10 mice in the 2-ME treated group had no tumor, whereas all control mice carried measurable tumors. Our data show that 2-ME is effective in the treatment of human hepatoma cells, which may be tumor specific.