Research Article

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

Figure 3

Dose-dependent inhibition of EGF-induced Erk 1/2 activation in U87MG (a), U87/EGFR (b) and U87/EGFRvIII (c) glioma cells. Serum-starved cells were treated with the indicated concentrations of Iressa ± mechlorethamine (HN2), ZRBA4 or ZR2003 for 2 h followed by a 20 min EGF (50 ng/mL) stimulation. Cell lysates (40 μg) were fractionated by SDS-PAGE and probed with anti-phospho-Erk 1/2 (1 : 1000) antibodies (see Materials and Methods for details). Blots were subsequently stripped and reprobed for total Erk 1/2 (1 :1000) followed by α-actinin (1:1500). Major protein bands of 44, 42 (Erk 1/2) and 100 kDa (α-actinin) were obtained.
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