Loss of programmed cell death 10 activates tumor cells and leads to temozolomide-resistance in glioblastoma
Glioblastoma (GBM) is one of the most aggressive and incurable primary brain tumors. Identification of novel therapeutic targets is an urgent priority. Programmed cell death 10 (PDCD10), a ubiquitously expressed apoptotic protein, has shown a dual function in different types of cancers and in chemo-resistance. Recently, we reported that PDCD10 was downregulated in human GBM. The aim of this study was to explore the function of PDCD10 in GBM cells.
PDCD10 was knocked down in three GBM cell lines (U87, T98g and LN229) by lentiviral-mediated shRNA transduction. U87 and T98g transduced cells were used for phenotype study and LN229 and T98g cells were used for apoptosis study. The role of PDCD10 in apoptosis and chemo-resistance was investigated after treatment with staurosporine and temozolomide. A GBM xenograft mouse model was used to confirm the function of PDCD10 in vivo. A protein array was performed in PDCD10-knockdown and control GBM cells.
Knockdown of PDCD10 in GBM cells promoted cell proliferation, adhesion, migration, invasion, and inhibited apoptosis and caspase-3 activation. PDCD10-knockdown accelerated tumor growth and increased tumor mass by 2.1-fold and led to a chemo-resistance of mice treated with temozolomide. Immunostaining revealed extensive Ki67-positive cells and less activation of caspase-3 in PDCD10-knockdown tumors. The protein array demonstrated an increased release of multiple growth factors from PDCD10-knockdown GBM cells.
Loss of programmed cell death 10 activates tumor cells and leads to temozolomide-resistance in GBM, suggesting PDCD10 as a potential target for GBM therapy.
KeywordsPDCD10/CCM3 Glioblastoma (GBM) GBM cell phenotype Apoptosis Chemo-resistance
The authors thank Dr. Anja Prinz and Dr. Kai Zhao for their contributions to establishing knockdown cell lines. We also thank Ms. Rita Haase for her technical assistance. X.Y.W. and Y.L.W. received a scholarship from the Medical Faculty, University of Duisburg-Essen. This study was supported financially by the IFORES-program at the Medical Faculty, University of Duisburg-Essen to Y.Z.
This study was supported financially by the IFORES-program at the Medical Faculty, University of Duisburg-Essen to Y.Z.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and /or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. The University of Duisburg-Essen approved all animal experiments (No. 84-02.04.2012.A348).
For this type of study formal consent is not required.
Research involving human and animal participants
This article does not contain any studies with human participants performed by any of the authors.
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