ArticleBMC cancer2006
Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction.
Article in BMC cancer, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 100 citations in OpenAlex.
- Shikonin treatment ameliorates lipopolysaccharide-induced acute liver failure in mice via regulating miR-106/MCL1 and miR-34a/SIRT1/TP53 signaling.Archives of medical science : AMS · 2026Article
- BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models.Nature cancer · 2024Article
- Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it.Exploration of targeted anti-tumor therapy · 2022Review
- Pivotal Role of Fatty Acid Synthase in c-MYC Driven Hepatocarcinogenesis.International journal of molecular sciences · 2020Article
- Gene Therapy with MiRNA-Mediated Targeting of Mcl-1 Promotes the Sensitivity of Non-Small Cell Lung Cancer Cells to Treatment with ABT-737.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Heterogeneity and Plasticity of Human Breast Cancer Cells in Response to Molecularly-Targeted Drugs.Frontiers in oncology · 2019Article
- Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas.Scientific reports · 2016Article
- A small interfering RNA targeting vascular endothelial growth factor efficiently inhibits growth of VX2 cells and VX2 tumor model of hepatocellular carcinoma in rabbit by transarterial embolization-mediated siRNA delivery.Drug design, development and therapy · 2016Article
- MicroRNA-302b Enhances the Sensitivity of Hepatocellular Carcinoma Cell Lines to 5-FU via Targeting Mcl-1 and DPYD.International journal of molecular sciences · 2015Article
- Reduced ubiquitin-specific protease 9X expression induced by RNA interference inhibits the bioactivity of hepatocellular carcinoma cells.Oncology letters · 2015Article
- Targeting mcl-1 for radiosensitization of pancreatic cancers.Translational oncology · 2015Article
- Ulinastatin reduces the resistance of liver cancer cells to epirubicin by inhibiting autophagy.PloS one · 2015Article
- Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells.Journal of Korean medical science · 2014Article
- Role of MicroRNAs in Hepatocellular Carcinoma.Hepatitis monthly · 2014Review
- Dynamic expression profiling of type I and type III interferon-stimulated hepatocytes reveals a stable hierarchy of gene expression.Hepatology (Baltimore, Md.) · 2014Article
- Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis.Journal of human genetics · 2014Article
- Overexpression of Mcl-1L splice variant is associated with poor prognosis and chemoresistance in oral cancers.PloS one · 2014Article
- Stearoyl-CoA desaturase plays an important role in proliferation and chemoresistance in human hepatocellular carcinoma.The Journal of surgical research · 2014Article
- Silence of MCL-1 upstream signaling by shRNA abrogates multiple myeloma growth.Experimental hematology & oncology · 2014Article
- New insights in hepatocellular carcinoma: from bench to bedside.Annals of translational medicine · 2013Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocelluar carcinoma (HCC) is one of the most common cancers worldwide and a major cause of cancer-related mortality. HCC is highly resistant to currently available chemotherapeutic drugs. Defects in apoptosis signaling contribute to this resistance. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which interferes with mitochondrial activation. In a previous study we have shown that Mcl-1 is highly expressed in tissues of human HCC. In this study, we manipulated expression of the Mcl-1 protein in HCC cells by RNA interference and analyzed its impact on apoptosis sensitivity of HCC cells in vitro.
methodsRNA interference was performed by transfecting siRNA to specifically knock down Mcl-1 expression in HCC cells. Mcl-1 expression was measured by quantitative real-time PCR and Western blot. Induction of apoptosis and caspase activity after treatment with chemotherapeutic drugs and different targeted therapies were measured by flow cytometry and fluorometric analysis, respectively.
resultsHere we demonstrate that Mcl-1 expressing HCC cell lines show low sensitivity towards treatment with a panel of chemotherapeutic drugs. However, treatment with the anthracycline derivative epirubicin resulted in comparatively high apoptosis rates in HCC cells. Inhibition of the kinase PI3K significantly increased apoptosis induction by chemotherapy. RNA interference efficiently downregulated Mcl-1 expression in HCC cells. Mcl-1 downregulation sensitized HCC cells to different chemotherapeutic agents. Sensitization was accompanied by profound activation of caspase-3 and -9. In addition, Mcl-1 downregulation also increased apoptosis rates after treatment with PI3K inhibitors and, to a lower extent, after treatment with mTOR, Raf I and VEGF/PDGF kinase inhibitors. TRAIL-induced apoptosis did not markedly respond to Mcl-1 knockdown. Additionally, knockdown of Mcl-1 efficiently enhanced apoptosis sensitivity towards combined treatment modalities: Mcl-1 knockdown significantly augmented apoptosis sensitivity of HCC cells towards chemotherapy combined with PI3K inhibition.
conclusionOur data suggest that specific downregulation of Mcl-1 by RNA interference is a promising approach to sensitize HCC cells towards chemotherapy and molecularly targeted therapies.
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