Abstract:
:The present study aimed to investigate the effect of NVP-BEP800, a novel heat shock protein (Hsp) 90 inhibitor of the 2-aminothieno[2,3-d]pyrimidine class, in combination with radiation on glioblastoma cells. T98G human glioblastoma cells were treated with dimethyl sulfoxide (DMSO), NVP-BEP800, NVP-BEP800 in combination with X-ray irradiation (10 Gy, 20 min), or X-ray irradiation only, and cultured for 40 h. Cell viability was measured upon completion of the treatments. In addition, apoptosis was measured and immunoblot analysis was performed to analyze the expression levels of cellular protein inhibitory κB kinase β (IKKβ). The combined treatment with NVP-BEP800 and X-ray irradiation resulted in the synergistic destruction of malignant cells. Furthermore, NVP-BEP800 significantly induced apoptosis in the human glioblastoma cells. The immunoblot analysis data indicated that NVP-BEP800 markedly reduced the expression level of IKKβ. The results also revealed that X-ray irradiation significantly attenuated the increase in the level of Hsp70 in cells treated with NVP-BEP800. Since elevated levels of Hsp70 are associated with drug resistance induced by Hsp90 inhibitors, the effects of X-ray irradiation on Hsp70 levels may be associated with the enhanced effect on cells of the presence of irradiation. The results of the current study suggest that irradiation enhances the inhibitory effect of NVP-BEP800 on the proliferation of malignant glioblastoma cells by downregulating the expression level of cellular signaling protein IKKβ and attenuating the upregulation of Hsp70 that is induced by NVP-BEP800.
journal_name
Exp Ther Medjournal_title
Experimental and therapeutic medicineauthors
Wu J,Wang W,Shao Q,Xiao G,Cheng J,Yuan Y,Zhang Mdoi
10.3892/etm.2014.1800subject
Has Abstractpub_date
2014-09-01 00:00:00pages
893-898issue
3eissn
1792-0981issn
1792-1015pii
etm-08-03-0893journal_volume
8pub_type
杂志文章abstract::The universal endocrine pathological state affecting young individuals and adults is type 2 diabetes mellitus, which has seen a significant increase in the last 30 years, particularly in children. Genetic and evnironmental factors are the causative agents for this pathological state in children. This rapid and wide sp...
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journal_title:Experimental and therapeutic medicine
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journal_title:Experimental and therapeutic medicine
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journal_title:Experimental and therapeutic medicine
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journal_title:Experimental and therapeutic medicine
pub_type: 杂志文章
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