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.
作者： Yun Yang , Ziyin Tian , Rui Guo , Feng Ren
DOI: 10.1155/2020/9867595
关键词: Protein kinase B 、 Transcription factor 、 Cancer cell 、 Apoptosis 、 Signal transduction 、 Medicine 、 Transfection 、 Cancer research 、 Antibody 、 Trastuzumab
摘要: The HER2-targeting antibody trastuzumab has shown effectiveness in treating HER2-positive breast and gastric cancers; however, its responses are limited. Currently, Nrf2 been deemed as a key transcription factor promoting cancer progression resistance by crosstalk with other proliferative signaling pathways. Brusatol novel inhibitor an efficacious safe drug candidate therapy. In this study, we firstly reported that brusatol exerted the growth-inhibitory effects on cells regressing Nrf2/HO-1 HER2-AKT/ERK1/2 pathways these cells. More importantly, found synergistically enhanced antitumor activity of against SK-OV-3 BT-474 cells, which may be attributed to inhibition Furthermore, synergistic were also observed tumor xenografts. addition, our results showed markedly brusatol-induced ROS accumulation apoptosis level, could further explain effects. To conclude, study provided new insight exploring combination HER2-targeted potential clinical treatment regimen cancers.
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