ArticleMolecular cancer2016
Efficient elimination of pancreatic cancer stem cells by hedgehog/GLI inhibitor GANT61 in combination with mTOR inhibition.
Article in Molecular cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Rewiring Cellular Context as A Central Mechanism Governing Cancer Stem Cell Survival: Insights from ESC Comparisons.Stem cell reviews and reports · 2026Review
- GANT61 suppresses proliferation and induces apoptosis in ALK-Positive anaplastic large cell lymphoma via modulating the Hh-PIK3IP1-Akt signaling axis.Annals of hematology · 2026Article
- Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.Medical oncology (Northwood, London, England) · 2025Review
- GLI2 inhibits cisplatin sensitivity in gastric cancer through DEC1/ZEB1 mediated EMT.Cell death & disease · 2025Article
- Targeted therapy of cancer stem cells: inhibition of mTOR in pre-clinical and clinical research.Cell death & disease · 2024Review
- Positive GLI1/INHBA feedback loop drives tumor progression in gastric cancer.Cancer science · 2024Article
- Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation.Current issues in molecular biology · 2024Review
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- Recent advances in drug delivery and targeting for the treatment of pancreatic cancer.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.Frontiers in pharmacology · 2024Review
- PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy.BMC cancer · 2023Article
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Palmitoyl transferases act as novel drug targets for pancreatic cancer.Journal of translational medicine · 2023Article
- Therapeutic role of mTOR inhibitors in control of SARS-CoV-2 viral replication.Molecular biology reports · 2023Review
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- GANT61 exerts anticancer cell and anticancer stem cell capacity in colorectal cancer by blocking the Wnt/β‑catenin and Notch signalling pathways.Oncology reports · 2022Article
- RNA-seq and ChIP-seq Identification of Unique and Overlapping Targets of GLI Transcription Factors in Melanoma Cell Lines.Cancers · 2022Article
- Hedgehog signaling regulates the development and treatment of glioblastoma.Oncology letters · 2022Review
- Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy.International journal of nanomedicine · 2022Review
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Authors and funding
7 authors.
Funding
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Abstract
backgroundPancreatic cancer is one of the most lethal malignancies. The innovative treatments are required and now the cancer stem cells (CSCs) are expected to be an effective target for novel therapies. Therefore we investigated the significance of hedgehog (Hh) signaling in the maintenance of CSC-like properties of pancreatic cancer cells, in order to discover the key molecules controlling their unique properties.
methodsHuman pancreatic cancer cell lines, Capan-1, PANC-1, MIA PaCa-2 and Capan-1 M9 were used for our experiments in DMEM/F12 medium containing 10 % fetal bovine serum. Sphere formation assay, immunofluorescence staining, flow cytometric analysis and MTT cell viability assay were performed to investigate molecular signals and the efficacy in the treatment of pancreatic cancer cells.
resultsInhibition of the Hh pathway significantly reduced the expression of stem cell marker CD133 and sphere formation, an index of self-renewal capacity, demonstrating the suppression of CSC-like properties. Moreover, the GLI inhibitor GANT61 induced greater reduction in sphere formation and cell viability of pancreatic cancer cells than the smoothened (SMO) inhibitor cyclopamine. This suggests that GLI transcription factors, but not SMO membrane protein, are the key molecules in the Hh pathway. The treatment using GANT61 in combination with the inhibition of mTOR, which is another key molecule in pancreatic CSCs, resulted in the efficient reduction of cell viability and sphere formation of an inhibitor-resistant cell line, showing the strong efficacy and wide range applicability to pancreatic CSC-like cells.
conclusionsThus, this novel combination treatment could be useful for the control of pancreatic cancer by targeting pancreatic CSCs. This is the first report of the efficient elimination of pancreatic cancer stem-like cells by the double blockage of Hh/GLI and mTOR signaling.
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