Glucose regulated protein 78 (GRP78) inhibits apoptosis and attentinutes chemosensitivity of gemcitabine in breast cancer cell via AKT/mitochondrial apoptotic pathway
| Autor: | JinFeng Zhang, Xichun Hu, Zheng-Hua Wu, Jie Xie, Ting Li, Jian Zhang, Zhonghua Tao, Jiang Zhao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Antimetabolites Antineoplastic Glucose-regulated protein Biophysics Apoptosis Breast Neoplasms Mitochondrion Caspase 8 Biochemistry Deoxycytidine 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine medicine Humans Molecular Biology Protein kinase B Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins Caspase-9 biology Dose-Response Relationship Drug Chemistry Cell Biology medicine.disease Gemcitabine Mitochondria 030104 developmental biology Endocrinology 030220 oncology & carcinogenesis Cancer research biology.protein MCF-7 Cells Proto-Oncogene Proteins c-akt medicine.drug Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 474(3) |
| ISSN: | 1090-2104 |
| Popis: | The underlying mechanism of gemcitabine resistance during breast cancer treatment remains unclear. Glucose regulated protein 78 (GRP78) frequently triggered by anticancer agents, was substantially elevated in gemcitabine resistant sublines. Ectopic expression of GRP78 changes gemcitabine chemosensitivity and apoptosis levels in breast cancer cells. Further experiments showed an involvement of caspase 9, not caspase 8, in gemcitabine resistance and GRP78-mediated chemosensitivity, suggesting that mitochondria apoptotic pathway was activated by GRP78. This finding was further supported by the observations of AKT activation, Bcl-2 increase, Bax and Bim decrease. Conclusively, GRP78 plays a vital role in gemcitabine resistance and clinical strategy to improve gemcitabine efficacy in breast cancer by manipulating GRP78 should be explored. |
| Databáze: | OpenAIRE |
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