title: Irradiation facilitates the inhibitory effect of the heat shock protein 90 inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through attenuation of the upregulation of heat shock protein 70.
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.
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Jianyue
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Guomin
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
keywords: NVP-BEP800; X-ray irradiation; glioblastoma; heat shock protein 70; heat shock protein 90 inhibitor