ArticleCancer chemotherapy and pharmacology2021
UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Acylcarnitines in Cancer Metabolism: Mechanistic Insights and Stratification Potential.Cancers · 2026Review
- Context-dependent roles of UCP2 in cancer: functional heterogeneity, molecular mechanisms and translational perspectives.Frontiers in oncology · 2026Review
- Epicatechin DecreasesInternational journal of molecular sciences · 2025Article
- Targeting mitochondrial quality control: new therapeutic strategies for major diseases.Military Medical Research · 2024Review
- UCP2 and pancreatic cancer: conscious uncoupling for therapeutic effect.Cancer metastasis reviews · 2024Review
- Diabetes Mellitus and Thyroid Cancers: Risky Correlation, Underlying Mechanisms and Clinical Prevention.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Unveiling the Role of the Proton Gateway, Uncoupling Proteins (UCPs), in Cancer Cachexia.Cancers · 2023Review
- UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control.International journal of molecular sciences · 2022Review
- Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature.International journal of molecular sciences · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThis study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment.
methods32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab.
resultsUCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis.
conclusionTaken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.
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