YB-1 modulates the drug resistance of glioma cells by activation of MDM2/p53 pathway
| Autor: | Kai Zhao, Jinxin Zhu, Hui Tong, Jianqi Xiao, Jingyu Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
p53
0301 basic medicine Cell Survival Pharmaceutical Science temozolomide Metastasis Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Glioma Drug Discovery medicine Humans Y-box binding protein-1 Viability assay Antineoplastic Agents Alkylating neoplasms Original Research Pharmacology Gene knockdown drug resistance Temozolomide Drug Design Development and Therapy Dose-Response Relationship Drug biology Chemistry Proto-Oncogene Proteins c-mdm2 Transfection medicine.disease 030104 developmental biology Real-time polymerase chain reaction Drug Resistance Neoplasm 030220 oncology & carcinogenesis biology.protein Cancer research Mdm2 Y-Box-Binding Protein 1 Tumor Suppressor Protein p53 Murine double minute 2 medicine.drug |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | Hui Tong,1,* Kai Zhao,2,* Jingyu Zhang,3 Jinxin Zhu,4 Jianqi Xiao2 1Department of Neurosurgery, Linyi Central Hospital, Linyi, Shandong 276400, People’s Republic of China; 2Department of Neurosurgery, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161005, People’s Republic of China; 3Department of Internal Medicine, Jiangpu District Health Center of Huai’an, Huai’an, Jiangsu, 223001, People’s Republic of China; 4Department of Neurosurgery, Lianshui County People’s Hospital, Huai’an, Jiangsu 223400, People’s Republic of China *These authors contributed equally to this work Background: Y-box-binding protein-1 (YB-1) is aberrantly expressed in a variety of cancers. However, the biological functional role of YB-1 in glioma is not yet clear. Methods: The expression of MDM2 and YB-1 was analyzed by real time PCR. Overexpression and knockdown of YB-1 in glioma cells were created by transfection of pcDNA-YB-1 and siRNA against YB-1, respectively. Cell viability was performed by CCK8 assay.Results: Our findings showed that glioma tissues had higher expressions of YB-1 than that in cancer-free tissues in 54 glioma patients, which were also positively correlated with Murine MDM2 expression. Overexpression of YB-1 or MDM2 renders a drug resistance feature in glioma cell exposed to temozolomide (TMZ), by directly targeting p53. Genetic or chemical inhibition of MDM2 significantly blocked YB-1-modulated response of glioma cells to TMZ. Moreover, inhibition of YB-1 or MDM2 reduced glioma cells metastasis and mortality in mice. Conclusion: YB-1 facilitates the resistance of glioma cells to TMZ by direct activation of MDM2/p53 signaling and represents a promising molecular target for glioma treatment. Keywords: glioma, p53, Murine double minute 2, Y-box binding protein-1, drug resistance, temozolomide |
| Databáze: | OpenAIRE |
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