ArticleBritish journal of cancer2017
Dasatinib synergises with irinotecan to suppress hepatocellular carcinoma via inhibiting the protein synthesis of PLK1.
Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- A Scalable and Robust Ensemble Deep Learning Method for Predicting Drug-Target Interactions.Interdisciplinary sciences, computational life sciences · 2026Article
- Thymoquinone-conjugated liposomes improve cytotoxic and proapoptotic effects against hepatocellular cancer by altering the EGFR/ERK/MEK signaling axis.Discover oncology · 2025Article
- Consensus artificial intelligence-driven prognostic signature for predicting the prognosis of hepatocellular carcinoma: a multi-center and large-scale study.NPJ precision oncology · 2025Article
- Human umbilical cord mesenchymal stem cell therapy for atopic dermatitis through inhibition of neutrophil chemotaxis.Stem cell research & therapy · 2025Article
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- Relationships Among Serological Indicators andCombinatorial chemistry & high throughput screening · 2025Article
- Combination of Phenethyl Isothiocyanate and Dasatinib Inhibits Hepatocellular Carcinoma Metastatic Potential through FAK/STAT3/Cadherin Signalling and Reduction of VEGF Secretion.Pharmaceutics · 2023Article
- Topoisomerase I Inhibition Radiosensitizing Hepatocellular Carcinoma by RNF144A-mediated DNA-PKcs Ubiquitination and Natural Killer Cell Cytotoxicity.Journal of clinical and translational hepatology · 2023Article
- An immune-related signature for optimizing prognosis prediction and treatment decision of hepatocellular carcinoma.European journal of medical research · 2023Article
- Editorial: Bioinformatics of genome regulation and systems biology, Volume III.Frontiers in genetics · 2023Article
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- Identification of m6A- and ferroptosis-related lncRNA signature for predicting immune efficacy in hepatocellular carcinoma.Frontiers in immunology · 2022Article
- PI3K/AKT/mTOR Pathway-Associated Genes Reveal a Putative Prognostic Signature Correlated with Immune Infiltration in Hepatocellular Carcinoma.Disease markers · 2022Article
- Role of 5-methylcytosine in determining the prognosis, tumor microenvironment, and applicability of precision medicine in patients with hepatocellular carcinoma.Frontiers in genetics · 2022Article
- Characterization of diagnostic and prognostic significance of cell cycle-linked genes in hepatocellular carcinoma.Translational cancer research · 2021Article
- Identification of prognostic long non-coding RNA signature with potential drugs in hepatocellular carcinoma.Aging · 2021Article
- Irinotecan-Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview.International journal of molecular sciences · 2020Review
- Irinotecan Induces Autophagy-Dependent Apoptosis and Positively Regulates ROS-Related JNK- and P38-MAPK Pathways in Gastric Cancer Cells.OncoTargets and therapy · 2020Article
- Multistage rocket: integrational design of a prodrug-based siRNA delivery system with sequential release for enhanced antitumor efficacy.Nanoscale advances · 2019Article
- Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma.OncoTargets and therapy · 2019Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is one of the most common types of malignant tumour and has poor prognosis. Currently, systematic chemotherapy is the only approach to prolong survival. Thus the development of new treatment regimens is urgently needed to improve the therapeutic efficacy. Our study intended to assess the combination of dasatinib and irinotecan against HCC and made an effort to develop a potential medical choice for advanced HCC patients.
methodsWe used SRB colorimetric assay and clonogenic assay to assess antitumour effect in vitro and HCC xenograft model to assess antitumour effect in vivo. We applied flow cytometry and western blotting to explore the mechanism of the combined therapy. Knockdown and overexpression of PLK1 are also applied for validation.
resultsWe confirmed that dasatinib has synergistic effect with irinotecan (or SN38) on HCC both in vitro and in vivo. The effect is due to arisen apoptosis rate of HCC cells that is accompanied by mitochondria dysfunction. The enhanced antitumour efficacy of SN38 could be explained by additional inhibition of PLK1, which is triggered by dasatinib. Unlike existed PLK1 inhibitors, dasatinib does not inhibit PLK1 activity in a direct way. Instead, we found that dasatinib reduces PLK1 level by interfering with its protein synthesis progress. We validated that this kind of downregulation of PLK1 level has a key role in the synergistic effect of the two agents.
conclusionsDasatinib is able to reinforce the anti-HCC efficacy of irinotecan/SN38 by downregulation of PLK1 synthesis. The combination of the two agents might be a potential medical choice for HCC therapy.
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