ArticleCellular oncology (Dordrecht, Netherlands)2019
Inhibition of MEK suppresses hepatocellular carcinoma growth through independent MYC and BIM regulation.
Article in Cellular oncology (Dordrecht, Netherlands), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Transglutaminases are oncogenic biomarkers in human cancers and therapeutic targeting of TGM2 blocks chemoresistance and macrophage infiltration in pancreatic cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Converged DNA Damage Response Renders Human Hepatocellular Carcinoma Sensitive to CDK7 Inhibition.Cancers · 2022Article
- Antitumor Efficacy of EGFR-Targeted Recombinant Immunotoxin in Human Head and Neck Squamous Cell Carcinoma.Biology · 2022Article
- Identification of Context-Specific Fitness Genes Associated With Metabolic Rearrangements for Prognosis and Potential Treatment Targets for Liver Cancer.Frontiers in genetics · 2022Article
- Emerging treatment modalities for systemic therapy in hepatocellular carcinoma.Biomarker research · 2021Review
- Mitogen-activated protein kinase inhibition-induced modulation of epidermal growth factor receptor signaling in human head and neck squamous cell carcinoma.Head & neck · 2021Article
- Efficacy, Tolerability, and Pharmacokinetics of Combined Targeted MEK and Dual mTORC1/2 Inhibition in a Preclinical Model of Mucosal Melanoma.Molecular cancer therapeutics · 2020Article
- LINC01419 promotes cell proliferation and metastasis in hepatocellular carcinoma by enhancing NDRG1 promoter activity.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- The MEK inhibitors enhance the efficacy of sorafenib against hepatocellular carcinoma cells through reducing p-ERK rebound.Translational cancer research · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is an aggressive malignancy. In HCC, mitogen-activated protein kinase (MAPK) signaling is overactivated. The MAPK kinase (MEK) inhibitor trametinib has been approved to treat several types of advanced cancers with a BRAF mutation. Herein, we examined whether trametinib has efficacy against HCC.
methodsThe effects of trametinib on cell viability, proliferation and tumor growth were assessed in HCC-derived cell lines and mouse xenograft models. Western blot analysis and immunohistochemistry were used to identify key regulators critical for HHC cell proliferation and tumor growth.
resultsWe found that trametinib dose-dependently inhibited the viability and proliferation of HCC cells. We also found that a strong suppression of MEK by trametinib downregulated the pro-survival protein MYC, but upregulated the pro-apoptotic protein BIM. This dual differential regulation of MYC and BIM was found to be accompanied by upregulation of a MYC-targeted cyclin dependent kinase inhibitor, p27
conclusionsCollectively, our data indicate that trametinib exhibits efficacy in treating HCC cells via distinct regulation of the MYC and BIM pathways. As such, targeting MEK to block MAPK signaling with trametinib may provide novel treatment opportunities for HCC.
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