NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies

Figure 4

NRF2 activation desensitises RTK signaling pathway to HER2 inhibitors Pertuzumab and Trastuzumab. (a) Immunoblot analysis showing tBHQ dependent recovery of RTK signaling following its inhibition by HER2 inhibitors. Exponentially growing cells were either left untreated (UT) or treated with combination of HER2 inhibitors, Pertuzumab and Trastuzumab at concentration of 20 μg/mL (RTKi), or with cotreatment of 200 μM tBHQ (RTKi + T) for 4 h before and processed for immunoblotting using relevant antibodies (Table 1). Ponceau stain of the same blot was used as loading control. (b) Bar chart showing total HER2, phospho-HER2, total HER3, phospho-AKT, phospho-ERK, phospho-NRF2, and BID levels in PEO1 and SKOV3 cell lines by quantifying immunoblot signal intensities obtained in (a) and normalised to the value of UT and expressed as fold change. Blue bars show ratio of phospho-HER2 to HER2 (upper panels) and cleaved BID to intact BID (lower panels).