ArticleScientific reports2019
Treatment with a new benzimidazole derivative bearing a pyrrolidine side chain overcomes sorafenib resistance in hepatocellular carcinoma.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- Heterocyclic Phytochemicals as Anticancer Agents.Current topics in medicinal chemistry · 2025Review
- Development of a machine learning-based model to predict prognosis of alpha-fetoprotein-positive hepatocellular carcinoma.Journal of translational medicine · 2024Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Nitric oxide/paclitaxel micelles enhance anti-liver cancer effects and paclitaxel sensitivity by inducing ferroptosis, endoplasmic reticulum stress and pyroptosis.RSC advances · 2023Article
- Novel 1,2,5-Trisubstituted Benzimidazoles Potentiate Apoptosis by Mitochondrial Dysfunction in Panel of Cancer Cells.ACS omega · 2022Article
- DYRK1A suppression attenuates HIF‑1α accumulation and enhances the anti‑liver cancer effects of regorafenib and sorafenib under hypoxic conditions.International journal of oncology · 2022Article
- Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets.Molecules (Basel, Switzerland) · 2021Review
- Imidazoles as Potential Anticancer Agents: An Update on Recent Studies.Molecules (Basel, Switzerland) · 2021Review
- A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives.Frontiers in pharmacology · 2021Review
- MDM2 Binding Protein Induces the Resistance of Hepatocellular Carcinoma Cells to Molecular Targeting AgentsFrontiers in oncology · 2021Article
- Treatment with a New Barbituric Acid Derivative Exerts Antiproliferative and Antimigratory Effects against Sorafenib Resistance in Hepatocellular Carcinoma.Molecules (Basel, Switzerland) · 2020Article
- Biological and Clinical Significance of the CCR5/CCL5 Axis in Hepatocellular Carcinoma.Cancers · 2020Article
- Iron-Catalyzed Acceptorless Dehydrogenative Coupling of Alcohols With Aromatic Diamines: Selective Synthesis of 1,2-Disubstituted Benzimidazoles.Frontiers in chemistry · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Currently, sorafenib is the standard first-line drug for patients with advanced HCC. However, long-term exposure to sorafenib often results in reduced sensitivity of tumour cells to the drug, leading to acquired resistance. Therefore, developing new compounds to treat sorafenib resistance is urgently needed. Although benzimidazole and its derivatives have been reported to exert antimicrobial and antitumour effects, the anti-drug resistance potential of these molecules is still unknown. In this study, we established sorafenib-resistant (SR) cell lines and an acquired sorafenib resistance xenograft model. We showed that treatment with a benzimidazole derivative bearing a pyrrolidine side chain (compound 9a) inhibited the proliferation of SR cells by blocking the phosphorylation of AKT, p70S6 and the downstream molecule RPS6. In addition, caspase 3/PARP-dependent apoptotic signals were induced in 9a-treated cells. Regarding epithelial-mesenchymal transition (EMT) activities, 9a treatment significantly suppressed the migration of SR cells. In particular, the levels of EMT-related transcription factors (snail, slug and twist) and mesenchymal markers (vimentin and N-cadherin) were downregulated. In the acquired sorafenib resistance xenograft model, compound 9a administration decreased the growth of tumours with acquired sorafenib resistance and the expression of the HCC markers α-fetoprotein, glypican 3 and survivin. In conclusion, treatment with this compound may be a novel therapeutic strategy for patients with sorafenib resistance.
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