The Concept of Divergent Targeting through the Activation and Inhibition of Receptors as a Novel Chemotherapeutic Strategy: Signaling Responses to Strong DNA-Reactive Combinatorial Mimicries

摘要: Recently, we reported the combination of multitargeted ErbB1 inhibitor–DNA damage combi-molecules with OCT in order to downregulate and activate SSTRs. Absence translation cell kill was believed be partially due insufficient blockage DNA damage. In this study, evaluated response molecules that more aggressively induce stronger attenuation phosphorylation. We used three lines expressing low levels (U87MG) or transfected overexpress wildtype (U87/EGFR) a variant (U87/EGFRvIII) ErbB1. The results showed Iressa±HN2 combi-molecules, ZRBA4 ZR2003, significantly blocked phosphorylation U87MG cells. Addition altered cycle distribution. Analysis pathway revealed strong upregulation p53 by HN2 combi-molecules. Apoptosis only induced 48 h exposure HN2. All other treatments resulted necrosis. This is agreement Akt-Bad activation survivin upregulation. Despite damaging properties downregulation these molecules, strongest effect SSTR on Therefore, any enhanced antiproliferative effects combining inhibition must addressed context arrest.