Anticancer efficacy and toxicity of oral GMO-paclitaxel in a hormone refractory prostate cancer model

Abstract

Purpose: We wanted to evaluate the efficacy and toxicity of the newly developed oral glyceryl monooleate (GMO)-paclitaxel in a hormone refractory prostate cancer model. Materials and methods: A paclitaxel formulation was prepared from GMO, tricaprylin, Tween®80 and paclitaxel. The tumor cells of prostate cancer (DU-145 cells) were incubated and then put into different paclitaxel concentrations. The tumoricidal activity was measured by using an indirect methylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay. Cells of the DU-145 cell line were subcutaneously heterotransplanted into 18 nude mice, and they developed prostate cancer. The 18 mice were divided into 3 groups; the control group was injected with the DU-145 cell line (n=6), the GMO group was injected with GMO after the DU-145 cells were injected (n=6), and the oral GMO-paclitaxel group was injected with oral GMO-paclitaxel after the DU-145 cells were injected (n=6). The tumor volume was measured every week and the main organs were evaluated pathologically to determine the toxicity. Results: On the MTT assay, the control group and the GMO group did not display cytotoxicity. However, treatment with the various GMO-paclitaxel formulations (0.1 μg/ml, 1 μg/ml, 10 μg/ml) for treating the DU-145 cell line cancer induced cytotoxicity in a dose dependent fashion. The tumor volumes were not significantly changed in the group that was administered oral GMO-paclitaxel. However, there were significantly increased tumor volumes in the control group and the GMO group (p< 0.05). Toxic changes were not detected in liver and kidney, and there was normal cellularity with a normal myeloid:erythroid ratio in the mice after the administration of oral GMO-paclitaxel. Conclusions: The newly developed oral GMO-paclitaxel has a remarkable cytotoxic effect against DU-145 cells without systemic toxicity. Therefore, oral GMO-paclitaxel therapy promises to be a safe and effective modality for treating hormone refractory prostate cancer, and it can possibly replace IV paclitaxel.