Response rate of fibrosarcoma cells to cytotoxic drugs on the expression level correlates to the therapeutic response rate of fibrosarcomas and is mediated by regulation of apoptotic pathways.

摘要: Because of the high resistance rate fibrosarcomas against cytotoxic agents clinical chemotherapy these tumors is not established. A better understanding diverse modes tumor cell death following therapies will provide a molecular basis for new chemotherapeutic strategies. In this study we elucidated response fibrosarcoma line to clinically used cytostatic on level gene expression. HT1080 cells were exposed doxorubicin, actinomycin D or vincristine. Total RNA was isolated and expression patterns analyzed by microarray analysis. Expression levels 46 selected candidate genes validated quantitative real-time PCR. The analysis data resulted in 3.309 (actinomycin D), 1.019 (doxorubicin) 134 (vincristine) probesets that showed significant changes. For synthesis blocker D, 99.4% all differentially expressed under-represented. comparison, down-regulated doxorubicin comprised only 37.4% effected agent. Closer regulated revealed induced mainly regulating abundance factors mediating mitochondrial (intrinsic) apoptosis pathway. Furthermore influences other pathways crosstalk (including receptor pathway) at multiple levels. We found increased cytochrome c, APAF-1 members STAT-family (STAT1, STAT3), while Bcl-2 decreased. Caspase-1, -3, -6, -8, -9 indicating proteases are key execution mediated apoptosis. This demonstrates regulates apoptosis-related cells. number specific pattern depend drug. rates level, i.e. drugs vincristine, correlate effectiveness drugs. Doxorubicin seems exert its mechanism genes, which involved several different pathways. exact knowledge affected help understand soft tissue sarcoma therapies.