Abstract 577: Combination therapy with arsenic trioxide and radiation in oral squamous carcinoma

Abstract

Abstract Objective: As a cancer therapeutic drug, arsenic trioxide (As2O3) was originally developed for promyelocytic leukemia. The emerging importance As2O3 in other solid tumors prompted extensive studies of mechanism of action of As2O3 in other types of cancer. Radiation is a commonly used therapeutic treatment for oral squamous carcinoma, while high dose radiation treatment is invasive with unwanted side effects. The aim of this study was to investigate if combined treatments with As2O3 and low dose radiotherapy could enhance the anti-tumor effects. Materials and Methods: Human oral squamous cell lines KB and Tca8113 and Human umbilical vein endothelial cells (HUVEC) were irradiated in vitro with a dose of 7.5Gy with or without low to high doses of As2O3. Cell survival was assessed by MTT assay. Flow cytometry was performed for the analysis of apoptosis. Tumor cell colony formation assay was detected in KB and Tca8113 cells and endothelial tube formation assay was evaluated in HUVEC. Nude mice xenografted animal model with oral cancer cells was established to evaluate the combination treatment efficacy of As2O3 and radiation. Results: As2O3 was able to enhanced radiation-induced tumor cell apoptosis and enhance radiation-induced inhibition of tumor cell proliferation and colony formation and endothelial cell tube formation. In vivo study, the combination treatment efficacy of As2O3 and radiation attained a significant decrease in the incidence of tumor development and tumor volume in nude mice. Conclusions: All these results suggested that As2O3 could enhance the therapeutic efficacy of low dose radiation treatment in vitro and in vivo in oral squamous carcinomas. 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 577.