ArticleMolecular and cellular biochemistry2019
Inhibition of sonic hedgehog and PI3K/Akt/mTOR pathways cooperate in suppressing survival, self-renewal and tumorigenic potential of glioblastoma-initiating cells.
Article in Molecular and cellular biochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- Review
- Exploring the Dual Roles of Neural Stem Cells in Glioblastoma: Therapeutic Implications and Opportunities.Current stem cell research & therapy · 2025Review
- Pharmacological Perspective on the Neurobiology of PI3K-Akt-mTOR Signalling in Opioid Dependence.CNS & neurological disorders drug targets · 2025Review
- Analysis of transcription profiles for the identification of master regulators as the key players in glioblastoma.Computational and structural biotechnology journal · 2024Article
- Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications.Molecular brain · 2024Review
- Review
- Article
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Crosstalk between glioblastoma and tumor microenvironment drives proneural-mesenchymal transition through ligand-receptor interactions.Genes & diseases · 2024Review
- Systems Medicine for Precise Targeting of Glioblastoma.Molecular biotechnology · 2023Review
- The Glioblastoma Landscape: Hallmarks of Disease, Therapeutic Resistance, and Treatment Opportunities.Medical research archives · 2023Article
- Re-Sensitizing Cancer Stem Cells to Conventional Chemotherapy Agents.International journal of molecular sciences · 2023Review
- Review
- Hedgehog signaling regulates the development and treatment of glioblastoma.Oncology letters · 2022Review
- Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy.Cancers · 2022Review
- Evaluation of Hedgehog Pathway Inhibitors as a Therapeutic Option for Uterine Leiomyosarcoma Using the Xenograft Model.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma.Frontiers in molecular neuroscience · 2022Review
- Apigenin Suppresses the Warburg Effect and Stem-like Properties in SOSP-9607 Cells by Inactivating the PI3K/Akt/mTOR Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Inhibition of Gli2 suppresses tumorigenicity in glioblastoma stem cells derived from a de novo murine brain cancer model.Cancer gene therapy · 2021Article
- SOX transcription factors and glioma stem cells: Choosing between stemness and differentiation.World journal of stem cells · 2021Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since PI3K/Akt/mTOR and sonic hedgehog (SHH) signaling pathways are highly activated in glioblastoma-initiating cells (GICs), we examined the effects of inhibiting these pathways on GIC characteristics and tumor growth in mice. NVP-LDE-225 (inhibitor of Smoothened) inhibited the expression of Gli1, Gli2, Smoothened, Patched1, and Patched2, and induced the expression of SuFu, whereas NVP-BEZ-235 (dual inhibitor of PI3K and mTOR) inhibited the expression of p-PI3K, p-Akt, p-mTOR, and p-p70S6K. NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting the self-renewal capacity of GICs, expression of pluripotency maintaining factors (Nanog, c-Myc, Oct4, and Sox2), Musashi1, cyclin D1, and Bcl-2, and transcription and expression of Gli, and in inducing the expression of cleaved caspase-3, cleaved PARP and Bim. Additionally, NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting epithelial-mesenchymal transition. Finally, the combination of NVP-LDE-225 and NVP-BEZ-235 was superior in inhibiting tumor growth, regulating the expression of pluripotency promoting factors, stem cell markers, cell cycle, and cell proliferation, and modulating EMT compared to single agent alone. In conclusion, the combined inhibition of PI3K/Akt/mTOR and SHH pathways was superior to single pathway inhibition in suppressing glioblastoma growth by targeting GICs.
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