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Proteomic alterations associated with acquired temozolomide resistance in human malignant gliomas:the potential role of prolyl 4-hydroxylase,beta polypeptide

Proteomic alterations associated with acquired temozolomide ...

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中国抗癌协会神经肿瘤专业委员会第八届学术会议

作者： Leung GKK Sun S Wong TS XQ Zhang Pu JKS lui wm Division of Neurosurgery Department of SurgeryLi Ka Shing Faculty of MedicineThe University of Hong KongQueen Mary Hospital

Introduction Temozolomide（TMZ） provides significant benefits in the treatment of malignant glioma but many patients continue to suffer from progressive or recurrent diseases due to their tumours’ intrinsic or acquired resistance to *** employed proteomic profiling to study the global protein expression changes in TMZ-resistant malignant glioma cell-lines,and investigate the potential role of one of the identified protein candidates,prolyl 4hydroxylase,beta polypeptide（P4HB）,that may be involved in the development of acquired *** Human malignant glioma cell-lines（D54 and U87） with acquired TMZ-resistance were first developed,and their biological behaviours were characterized before protein profiling analysis by two dimensional gel electrophoresis（2DE）.Potential protein spot candidates were identified by MALDI-TOF/*** transfection with small interfering RNAs was used to knock down potential candidates to study their biological *** A total of 15 spots were identified as the most highly up-or down-regulated proteins in TMZ-resistant glioma *** these,the protein P4HB was found to be consistently dysregulated in D54 sublines of different levels of TMZ-resistance when compared to their TMZ-sensitive parental and the passage control *** expression of P4HB transcripts and proteins were also confirmed in U87 cells by qPCR and western blotting *** knock-down was found to significantly down-regulate P4HB expression,and increase TMZ-induced *** P4HB is known to play an important role in hypoxia-induced cell *** present study is the first to describe its role in the regulation of apoptosis in TMZ-treated malignant glioma cells and the development of acquired TMZ-resistance.P4HB is a potential candidate for future studies in TMZ-induced cytotoxicity and novel therapeutic strategies for the treatment of TMZ-resistant malignant glioma.

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