ReferenceID 4759
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
Oxid Med Cell Longev
The HER2-targeting antibody trastuzumab has shown effectiveness in treating HER2-positive breast and gastric cancers; however, its responses are limited. Currently, Nrf2 has been deemed as a key transcription factor in p
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4759
- Evidence Id
- 21349
- Core Evidence Id
- 21349
- Source Reference Id
- 2755
- Herb2 Reference Id
- HBREF003552
- Subject Paper Key
- HBIN018930_32765809
- Pubmed Id
- 32765809
- Doi
- 10.1155/2020/9867595
- Paper Title
- 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
- Paper Abstract
- The HER2-targeting antibody trastuzumab has shown effectiveness in treating HER2-positive breast and gastric cancers; however, its responses are limited. Currently, Nrf2 has been deemed as a key transcription factor in promoting cancer progression and resistance by crosstalk with other proliferative signaling pathways. Brusatol as a novel Nrf2 inhibitor has been deemed as an efficacious and safe drug candidate in cancer therapy. In this study, we firstly reported that brusatol exerted the growth-inhibitory effects on HER2-positive cancer cells by regressing Nrf2/HO-1 and HER2-AKT/ERK1/2 signaling pathways in these cells. More importantly, we found that brusatol synergistically enhanced the antitumor activity of trastuzumab against HER2-positive SK-OV-3 and BT-474 cells, which may be attributed to the inhibition of Nrf2/HO-1 and HER2-AKT/ERK1/2 signaling pathways. Furthermore, the synergistic effects were also observed in BT-474 and SK-OV-3 tumor xenografts. In addition, our results showed that trastuzumab markedly enhanced brusatol-induced ROS accumulation and apoptosis level, which could further explain the synergistic effects. To conclude, the study provided a new insight on exploring Nrf2 inhibition in combination with HER2-targeted trastuzumab as a potential clinical treatment regimen in treating HER2-positive cancers.
- Journal
- Oxid Med Cell Longev
- Publish Year
- 2020
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Breast And Gastric Cancers; Tumor; Cancer; Her2-positive Cancers
- Paper Title Cn
- Paper Title En
- 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
- Bilingual Status
- semi_complete