Nrf2 Inhibitor, Brusatol in Combination with Trastuzumab Exerts Synergistic Antitumor Activity in HER2-Positive Cancers by Inhibiting Nrf2/HO-1 and HER2-AKT/ERK1/2 Pathways

<div>Nrf2 inhibition resulted in repression of HER2-AKT/ERK1/2 signaling and sensitizes SK-OV-3 cells to trastuzumab treatment. (a) The level of p-HER2, p-AKT, and p-ERK1/2 were determined after treatment with Nrf2-targeted siRNA or scramble siRNA for 36 h. (b) Cell viability was monitored after trastuzumab (50 <i>μ</i>g/mL) incubation for 24 h in scramble siRNA or Nrf2 siRNA-transfected cells. Cells were transfected with scramble siRNA or Nrf2 siRNA using Lipofectamine 2000 (Invitrogen) according to the supplier’s instruction. 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304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g></svg> (three independent experiments). <span class="nowrap"><svg height="11.7782pt" id="M28" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 59.8454 11.7782" width="59.8454pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M471 153C471 170 463 194 452 212C400 220 373 229 322 255C373 281 400 290 452 298C463 316 471 339 471 357C456 366 431 371 410 370C377 329 356 310 308 279C311 336 317 364 336 413C326 432 310 451 294 459C279 451 262 432 252 413C271 364 277 336 280 279C232 310 211 329 178 370C157 371 132 367 117 357C117 340 125 316 136 298C188 290 215 281 266 255C215 229 188 220 136 212C125 194 117 171 117 153C132 144 157 139 178 140C211 181 232 200 280 231C277 174 271 146 252 97C262 78 278 59 294 51C309 59 326 78 336 97C317 146 311 174 308 231C356 200 377 181 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Oxidative Medicine and Cellular Longevity

fig4

Figure 4

Figure 4: Nrf2 Inhibitor, Brusatol in Combination with Trastuzumab Exerts Synergistic Antitumor Activity in HER2-Positive Cancers by Inhibiting Nrf2/HO-1 and HER2-AKT/ERK1/2 Pathways 

Figure 4 | Nrf2 Inhibitor, Brusatol in Combination with Trastuzumab Exerts Synergistic Antitumor Activity in HER2-Positive Cancers by Inhibiting Nrf2/HO-1 and HER2-AKT/ERK1/2 Pathways 