The temozolomide derivative 2T-P400 inhibits glioma growth via administration route of intravenous injection

Abstract

The aim of this study is to investigate the inhibitory effects of 2T-P400, a derivative of temozolomide (TMZ), on glioma growth. SHG-44 and U373 human glioblastoma cell lines and SHG-44 cell subcutaneous and intracranial xenograft mouse models were used as the model system for these studies. Cell growth was analyzed using MTT assay. For intracranial glioma xenograft model, mouse brains were obtained and made as paraffin section for immunohistochemical staining. Tumor volume was calculated with this formula: tumor volume = length × width2/ 2. The results showed that 2T-P400 or TMZ significantly inhibits cell growth in a concentration dependent manner with the IC50 values of 12.90 ± 1.05 or 9.73 ± 2.12 μg/ml on SHG-44 cell line and 13.12 ± 0.86 or 10.13 ± 1.02 μg/ml on U373 cell line respectively. In SHG-44 cell subcutaneous xenograft model, the tumor volume of 2T-P400 or TMZ treated group was 1,062.12 ± 204.76 or 803.59 ± 110.32 mm3 respectively, which was significantly smaller than that in physiological saline (with volume of 1,968.85 ± 348.37 mm3) treated group. In intracranial xenograft model, the tumor volume of 2T-P400 or TMZ group was 6.12 ± 1.69 or 5.58 ± 1.45 mm3 respectively, significantly smaller than that in physiological saline group of 33.08 ± 6.88 mm3. Moreover, polyethylene glycol 400 (PEG400) exhibited no significant tumor growth inhibition. Our results indicated that 2T-P400 posses the same growth inhibitory effect as TMZ on glioblastoma cell lines and the subcutaneously and intracranially transplanted gliomas in xenograft mouse models. It may be a suitable alternate of TMZ for the treatment of glioma via intravenous administration route.