Trabectedin

Trabectedin (Ecteinascidin 743, ET-743) is a marine alkaloid isolated from the Caribbean tunicate Ecteinascidia turbinata with antitumour activity. Trabectedin binds to the N2 of guanine in the minor groove, causing DNA damage and affecting transcription regulation in a promoter- and gene-specific manner.

Trabectedin can block EWS-FLI1 transcription factor activity, suppress Werner syndrome protein (WRN) expression and selectively sensitize Ewing sarcoma cells to the DNA-damaging effects of SN38. ^{<a class="sref" href="#s_ref">[1]</a>}^{<a class="sref" href="#s_ref">[3]</a>}

RNAiMax Lipofectamine (4.5 mL per well in a 6-well dish) was added to siRNA targeting the EWS-FLI1 breakpoint site II, complexed, combined with cells, and incubated for 36 to 48 hours before collection for Western blot analysis.

In Tumor-Bearing Mice, trabectedin does not have an impact on the functional activity of MDSC but does significantly reduce the number of Ly6C^high cells, the most suppressive subset. ^{<a class="sref" href="#s_ref">[4]</a>}