Eur Rev Med Pharmacol Sci 2020; 24 (17): 8918-8930

DOI: 10.26355/eurrev_202009_22833

FKBP51 acts as a biomarker of early metastasis and is related to carmustine sensitivity in human glioma cells

H. Li, Y.-L. Jiao, R.-F. Zhou, S. Liu, B. Cui, L.-C. Wang, X.-W. Liu, Y.-R. Zhao

Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China. lxmfmmu@sina.com


OBJECTIVE: Given that FK506 binding protein 51 (FKBP51) is upregulated in multiple cancers, we designed the present study to characterize its role as well as underlying regulatory mechanisms in glioma in the presence and absence of the chemotherapeutic carmustine (BCNU).

MATERIALS AND METHODS: Through lentiviral overexpression and shRNA knockdown of FKBP51, we examined the effects on BT325 glioma cell proliferation, migration and invasion using quantitative reverse transcription PCR (qRT-PCR), CCK-8 assay, flow cytometry, and transwell assay.

RESULTS: The upregulation of FKBP51 resulted in significantly decreased BT325 cell proliferation and cell viability, cell cycle arrest, reduced BCNU chemosensitivity and AKT pathway inactivation. However, FKBP51-overexpressed BT325 cells showed enhanced migration and invasion, which was supported by corresponding increase in phosphorylated IKKα (p-IKKα), MMP-2, and MMP-9 levels, as well as increased NF-κB p65 nuclear translocation. By contrast, FKBP51-suppressed BT325 cells showed excessive proliferation and BCNU resistance due to increased p-AKT activation and attenuated migration and invasion.

CONCLUSIONS: We demonstrated that the effects of FKBP51 on BT325 glioma cell proliferation, migration, invasion and BCNU chemosensitization are modulated via the AKT and NF-κB pathways. Furthermore, our findings suggest the potential of FKBP51 as a prognostic glioma biomarker and an indicator of patient response to chemotherapy.

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H. Li, Y.-L. Jiao, R.-F. Zhou, S. Liu, B. Cui, L.-C. Wang, X.-W. Liu, Y.-R. Zhao
FKBP51 acts as a biomarker of early metastasis and is related to carmustine sensitivity in human glioma cells

Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 17
Pages: 8918-8930
DOI: 10.26355/eurrev_202009_22833