gms | German Medical Science

Introduction: With a maximum response rate of only 20% cytostatics have a low effect on Liposarcoma. In clinical everydays practice cytostatics are not established for curative treatment and their use is restricted to clinical studies. Besides Ifosfamide Doxorubicin is considered the most potent substance. In this study, the effects of Doxorubicin on human liposarcoma on gene expression level are analyzed.

Material and Methods: 19 human Liposarcoma cell lines were brought into cell culture and incubated with doxorubicin (0.5mg/ml). After 6 and 24 h RNA was isolated and gene expression was analyzed by cDNA-Microarrays (Affimetrix, 14.500 genes). Selected responder genes were further studied using Gene Ontology (GO)-Analysis and Bonferroni correction.

Results: According to the number of responding genes the 19 liposarcomas were categorized high, intermediate and low responders. All poorly differentiated (GIII) tumors were high responders, GII tumors were predominantly intermediate responders and GI tumors were mostly low responders. The pathways that were differently regulated included immunological processes, probably stimulated by the in vitro cultivation, cell communication, cell proliferation, DNA replication and cell death. The response patterns were very heterogenous. Only in poorly differentiated tumors cell death regulating genes were markedly overexpressed. Conclusion: Liposarcoma cells showed specific individual RNA expression patterns after incubation with doxorubicin. Despite a correlation of the number of differentially regulated genes to the tumor grading, the expression patterns are very heterogenous. A definite effect on apoptotic pathways was seen only in poorly differentiated liposarcomas. This study shows that decoding the molecular genetics of cytostatic effects can explain clinical effects and may be a promising approach to improve response rates.