Abstract:
BACKGROUND:Intratumoural hypoxia is associated with chemoresistance in glioblastoma multiforme (GBM), a highly malignant brain tumour. Adaptive response to endoplasmic reticulum stress induced by temozolomide is a major obstacle in recurrent GBM. We investigated whether hyperoxia resensitizes temozolomide-resistant GBM cells to temozolomide by abrogating the hypoxia-induced, unfolded protein response (UPR)-related protective mechanisms. MATERIALS AND METHODS:We examined changes to key UPR modulators in temozolomide-sensitive and -resistant human GBM cells (D54 and U87) treated with/without temozolomide at different oxygen concentrations using western blotting, and cytotoxic benefits of overexpressing key chaperone, P4HB, in GBM cells (U87 and U251) under normoxia and hyperoxia. RESULTS:Hyperoxia, alone or synergistically with temozolomide, activated the UPR in sensitive and resistant D54 and U87 cell lines. Hyperoxia also reduced survival benefit of U87 and U251 cells with P4HB overexpression through the UPR. CONCLUSION:Hyperoxia enhanced GBM cell sensitivity to temozolomide, likely through UPR, highlighting an important treatment modality targeting chemosensitive and -resistant GBM.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Lee D,Sun S,Ho AS,Kiang KM,Zhang XQ,Xu FF,Leung GKsubject
Has Abstractpub_date
2014-06-01 00:00:00pages
2957-66issue
6eissn
0250-7005issn
1791-7530pii
34/6/2957journal_volume
34pub_type
杂志文章abstract:BACKGROUND/AIM:Only 0.1-0.17% of all lung cancer patients are diagnosed with stage I or II small cell lung cancer (SCLC). Radiochemotherapy remains the standard treatment for limited stage disease. This study focused on prognostic factors in early stage SCLC treated with radiochemotherapy. PATIENTS AND METHODS:Seven f...
journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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doi:
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journal_title:Anticancer research
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doi:
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journal_title:Anticancer research
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更新日期:2015-05-01 00:00:00
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doi:
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
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更新日期:2007-11-01 00:00:00
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journal_title:Anticancer research
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doi:
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更新日期:2013-09-01 00:00:00
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更新日期:2002-01-01 00:00:00
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journal_title:Anticancer research
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doi:
更新日期:2011-10-01 00:00:00
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更新日期:2017-09-01 00:00:00
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journal_title:Anticancer research
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doi:
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