Abstract
Abstract: :
Purpose: Targretin (bexarotene) is a synthetic retinoid that has demonstrated significant anticancer effects in animal tumor models and in clinical trials of cancer patients. We investigated the potential utility of Targretin in the clinical management of retinoblastoma. Methods: Antiproliferative effects of Targretin were evaluated in human retinoblastoma cells in vitro. Two established retinoblastoma cell lines, Y79 and Weri–RB1, were treated with Targretin at concentrations ranging from 0.1 to 20uM. At 96 hours post–treatment, antiproliferative effects were determined by WST–1 Cell Proliferation Assay (Roche). All assays were performed in triplicate. Results were converted into live cell counts using standard curves and expressed as percent viability. Results were considered optimal if the concentration required to induce 50% growth inhibition (IC50) fell within clinically achievable levels. Results: At 96 hours post–treatment, Targretin demonstrated mild antiproliferative effects that were not dose–dependent. This retinoid induced a maximum cell growth inhibition of approximately 18% in Y79 cells and 45% in Weri–RB1 cells at clinically achievable concentrations. Targretin failed to induce an IC50 at all concentrations tested. Conclusions: Although Targretin was ineffective at inhibiting retinoblastoma cell growth by 50%, this agent did demonstrate mild antiproliferative effects in Y79 and Weri–RB1 cell lines at clinically relevant concentrations. Therefore, Targretin could have clinical utility as an adjuvant in current retinoblastoma therapy. Retinoids have the potential to increase treatment efficacy and to reduce total chemotherapeutic exposure in patients with this cancer predisposition syndrome.
Keywords: retinoblastoma • tumors • oncology