ReferenceID 5070
Cyclopamine sensitizes glioblastoma cells to temozolomide treatment through Sonic hedgehog pathway
Life Sci
AIM: Glioblastoma is an extremely aggressive glioma, resistant to radio and chemotherapy usually performed with temozolomide. One of the main reasons for glioblastoma resistance to conventional therapies is due to the pr
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Record Fields
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- Reference Id
- 5070
- Evidence Id
- 21660
- Core Evidence Id
- 21660
- Source Reference Id
- 3416
- Herb2 Reference Id
- HBREF004213
- Subject Paper Key
- HBIN022330_32622951
- Pubmed Id
- 32622951
- Doi
- 10.1016/j.lfs.2020.118027
- Paper Title
- Cyclopamine sensitizes glioblastoma cells to temozolomide treatment through Sonic hedgehog pathway
- Paper Abstract
- AIM: Glioblastoma is an extremely aggressive glioma, resistant to radio and chemotherapy usually performed with temozolomide. One of the main reasons for glioblastoma resistance to conventional therapies is due to the presence of cancer stem-like cells. These cells could recapitulate some signaling pathways important for embryonic development, such as Sonic hedgehog. Here, we investigated if the inhibitor of the Sonic hedgehog pathway, cyclopamine, could potentiate the temozolomide effect in cancer stem-like cells and glioblastoma cell lines in vitro. MAIN METHODS: The viability of glioblastoma cells exposed to cyclopamine and temozolomide treatment was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while the induction of apoptosis was assessed by western blot. The stemness properties of glioma cells were verified by clonogenic and differentiation assay and the expression of stem cell markers were measured by fluorescence microscopy and western blot. KEY FINDINGS: The glioblastoma viability was reduced by cyclopamine treatment. Cyclopamine potentiated temozolomide treatment in glioblastoma cell lines by inducing apoptosis through activation of caspase-3 cleaved. Conversely, the combined treatment of cyclopamine and temozolomide potentiated the stemness properties of glioblastoma cells by inducing the expression of SOX-2 and OCT-4. SIGNIFICANCE: Cyclopamine plays an effect on glioblastoma cell lines but also sensibilize them to temozolomide treatment. Thus, first-line treatment with Sonic hedgehog inhibitor followed by temozolomide could be used as a new therapeutic strategy for glioblastoma patients.
- Journal
- Life Sci
- Publish Year
- 2020
- Experiment Subject
- patient; cancer stem-like cells; glioblastoma cell lines
- Experiment Type
- Cell Experiment
- Phenotype Related
- Glioblastoma; Glioma; Cancer
- Paper Title Cn
- Paper Title En
- Cyclopamine sensitizes glioblastoma cells to temozolomide treatment through Sonic hedgehog pathway
- Bilingual Status
- semi_complete