gms | German Medical Science

Objective: Fatty Acid Synthasis (FAS) is one of the key enzymes for synthesizing new fatty acids and is overexpressed in a variety of carcinomas. For Orlistat as an inhibitor of FAS, antitumor effects could already be detected in different tumor entities. In cell cultures of glioblastoma reduction of cell growth has also been shown. Now these results should be reevaluated in a mouse model.

Methods: To investigate the antitumoral effects of Olistat on glioblastomas, cells of line A172 were xenografted into flanks of NOD.CB17-Prkdcscid/NCrHsd mice. Subsequently, an initial size of transplanted cells in mice was measured by MRI (3T, Siemens). The volume determination was carried out with a DICOM image processing software (Osirix). Before randomization and treatment, a new measurement was performed to determine the growth. The mice were randomized into 3 groups. 1. Orlistat (240 mg/kg bodyweight) and vehicle (PEG, ethanol, NaCl solution), 2. vehicle only and 3. a control group. After four weeks of treatment, a final volume determination was performed. Afterwards, the tumor samples were prepared from the deadened mice and analyzed by Western-Blot-analysis for pro-apoptotic proteins (FAS, Caspase8, Apaf, Caspase3 and PARP).

Results: Tumor size was defined as 100% before treatment, after four-week treatment period, size changes were included in the data as a percentage change against start of treatment. If data are compared, an increase of tumor volume independent of the treatment can always be determined in median. It shows largest increase in the control group with about 50% growth. Looking at the orlistat and vehicle group, it can be seen that the Orlistat group has grown 18% and in vehicle group 10% growth only in median approximately. Western blots exhibit a correlation between expression of pro-apoptotic proteins and growth in differenced groups with increasing signals for FAS, Caspase8 and Apaf in the Orlistat group rather than the vehicle alone. At least highest expression of uncleaved PARP is verified in the vehicle group followed by the others.

Conclusion: Largest increase is observed in untreated control group. The Orlistat and vehicle group show a better growth inhibition and indexing of apoptotic cascade than those without treatment. Results emerge no objective difference in antiproliferative and proapoptotic effects against glioblastomas among treatment with vehicle only or orlistat additionally in mouse model.