ReferenceID 5916
Oroxylin A reversed Fibronectin-induced glioma insensitivity to Temozolomide by suppressing IP3R1/AKT/β-catenin pathway
Life Sci
AIMS: Cell adhesion mediated-drug resistance (CAM-DR) is one of main reasons for. the limitation to chemotherapy, but the underlying mechanism remains unclear in glioma. In this study, we investigated the mechanism of CA
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Record Fields
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- Reference Id
- 5916
- Evidence Id
- 22506
- Core Evidence Id
- 22506
- Source Reference Id
- 5089
- Herb2 Reference Id
- HBREF005886
- Subject Paper Key
- HBIN038303_32918978
- Pubmed Id
- 32918978
- Doi
- 10.1016/j.lfs.2020.118411
- Paper Title
- Oroxylin A reversed Fibronectin-induced glioma insensitivity to Temozolomide by suppressing IP3R1/AKT/β-catenin pathway
- Paper Abstract
- AIMS: Cell adhesion mediated-drug resistance (CAM-DR) is one of main reasons for. the limitation to chemotherapy, but the underlying mechanism remains unclear in glioma. In this study, we investigated the mechanism of CAM-DR induced by Fibronectin (Fn). Besides, we studied the reversal effect of Oroxylin A, a natural flavonoid extracted from Scutellaria radix, on Temozolomide (TMZ) insensitivity of glioma cells. MAIN METHODS: Human Fn protein was used to mimic cell adhesion model and investigate its effect on the insensitivity of glioma cells to TMZ. Moreover, Oroxylin A was studied regarding its reversal effect on TMZ insensitivity of glioma via multiple molecular biological methods such as MTT, cell apoptosis assay, siRNA transfection, western blot, immunofluorescence assay. KEY FINDINGS: Fn could decrease the apoptosis-inducing effect of TMZ and led to the CAM-DR in glioma cells. Further studies showed that up-regulations of IP3R1 and intracellular Ca2+ level induced the activation of AKT kinase which increased the phosphorylation of GSK-3beta and subsequently caused the entry of beta-catenin into the nucleus. Knocking down IP3R1 significantly improved the sensitivity of glioma cells to TMZ. Meanwhile, after treatment with low-toxic concentration of Oroxylin A, the apoptosis induced by TMZ under Fn condition increased dramatically. Furthermore, our results revealed that Oroxylin A markedly inhibited the expression of IP3R1 and the activation of AKT/beta-catenin pathway. SIGNIFICANCE: Oroxylin A could reverse the insensitivity of TMZ via suppressing IP3R1/AKT/beta-catenin pathway and it might be helpful for enhancing the anti-cancer effect of TMZ in glioma.
- Journal
- Life Sci
- Publish Year
- 2020
- Experiment Subject
- human
- Experiment Type
- Cell Experiment
- Phenotype Related
- Oroxylin; Glioma
- Paper Title Cn
- Paper Title En
- Oroxylin A reversed Fibronectin-induced glioma insensitivity to Temozolomide by suppressing IP3R1/AKT/β-catenin pathway
- Bilingual Status
- semi_complete