Rbio-03. improving gemcitabine-mediated radio-sensitization using molecularly targeted meningioma therapy

BACKGROUND:Of the many treatment options, gemcitabine has been currently used clinically to a variety of solid tumors types both as a chemotherapeutic agent and as a radiation sensitizer. However, it has been speculated that the gemcitabine plus relatively high dose of radiation increased the toxicity. Therefore, our current approaches to integrate of molecularly targeted agents, which potentially produce less toxicity than standard chemotherapy, and with gemcitabine-radiation improve chemo-radiation sensitivity.METHODS:We combined HDACs or Chk1 inhibitors with gemcitabine and radiation using three meningioma cell lines (Ben Men 1, CH157 MN, and IOMM-Lee). These cell lines were treated with the 1 µM of HDAC inhibitor (Ganoderic Acid A and DM) or 1 µM of Chk1 inhibitor (UCN-01 and SB218078) with 1 µM of gemcitabine plus irradiation (1 Gy single dose) for 72 hr. Cell proliferation (SRB assay), cell survival (clonogenic assay) and apoptosis (Western blot) were analyzed following treatments.RESULTS:Our in vitro studies demonstrated that HDAC inhibitors Ganoderic Acid (A and DM) andChk1 inhibitor UCN-01 and SB218078 enhances gemcitabine + radiation activity, likely via disruption of HDAC activities and Chk1 signaling and inducing caspase-3 activities. These studies also indicate that timing of drug administration strongly influences response to gemcitabine + radiation activity plus HDAC inhibitor or Chk1 inhibitor in all three meningioma cells...

Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Das, A., McDonald, D. G., Alexander Vandergrift, W., Varma, A. K., Lindhorst, S. M., Raizer, J., Giglio, P., Patel, S. J., Decandio, M. L., Banik, N. L., Vanek, K. N., Jenrette, J. M., Cachia, D. Tags: RADIOBIOLOGY Source Type: research