MTR-06A STRATEGY FOR REDUCING HYPOXIA INDUCED CHEMORESISTANCE IN GLIAL CELLS
| العنوان: | MTR-06A STRATEGY FOR REDUCING HYPOXIA INDUCED CHEMORESISTANCE IN GLIAL CELLS |
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| المؤلفون: | Subrata Sinha, Ajay Yadav, Akansha Jalota, Bhudev C. Das, Kunzang Chosdol |
| المصدر: | Neuro-Oncology. 17:v125.2-v125 |
| بيانات النشر: | Oxford University Press (OUP), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Cancer Research, Autophagy, Caspase 3, Biology, Cell cycle, medicine.disease, Molecular biology, chemistry.chemical_compound, Oncology, chemistry, Apoptosis, Glioma, Unfolded protein response, medicine, Cancer research, MTT assay, Neurology (clinical), Propidium iodide, Abstracts from the 20th Annual Scientific Meeting of the Society for Neuro-Oncology |
| الوصف: | BACKGROUND: Glioblastoma multiforme is refractory to conventional treatment, highlighting the need for more efficient therapies. Hypoxia, which is a characteristic feature of glioma is markedly responsible for the chemoresistance. A rational combination of drugs has the possibility of improving therapeutic response. Cisplatin (CP) and 2- Deoxy-D-glucose (2-DG) are not very effective as single agents, and hence we have investigated the efficacy and mechanism of action of their combination in glial tumor cell lines, under both normoxia and hypoxia. METHODS: Cell survival analysis after treatment with combination as compared to single agent was done by MTT assay and combination index calculated. MTT results were confirmed through caspase 3/7 assay and propidium iodide staining. Expression of autophagy, apoptosis, endoplasmic reticulum (ER) stress markers were confirmed through Real time PCR and western blotting. ATP assay was done to investigate the effect on cellular metabolism. RESULTS: The combination of CP and 2-DG was synergistic under normoxia and hypoxia with combination index less than 1. Analysis of caspase 3/7 activity and cell cycle (subG1) along with biomarkers of autophagy and apoptosis indicated switch over from autophagic to apoptotic pathways. Since 2-DG induces autophagy through ER stress, reduction in autophagy by the combination was further confirmed by reduction in ER stress marker under both normoxia and hypoxia. CONCLUSION: The in-vitro study showed the potential of the combination for reducing chemoresistance under both normoxia and hypoxia in glioma cells. Abrogation of the chemoresistance by the combination was through attenuation of autophagy by reduction in ER stress. |
| تدمد: | 1523-5866 1522-8517 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b62c8e7f40c313f29530ef09576a57a8Test https://doi.org/10.1093/neuonc/nov219.06Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b62c8e7f40c313f29530ef09576a57a8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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