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01.08.2011 | Laboratory Investigation - Human/Animal Tissue

PTEN restoration and PIK3CB knockdown synergistically suppress glioblastoma growth in vitro and in xenografts

verfasst von: Hongbo Chen, Lin Mei, Lanzhen Zhou, Xiaomeng Shen, Caiping Guo, Yi Zheng, Huijun Zhu, Yongqiang Zhu, Laiqiang Huang

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2011

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Abstract

Glioblastoma is the most frequent and malignant glioma in adults. To develop an effective gene therapy strategy for glioblastoma, we investigated the anti-proliferative effects of phosphatase and tensin homolog (PTEN) restoration and siRNAs specifically targeting PIK3CB and PIK3CA on PTEN-deficient glioblastoma cells in vitro and in subcutaneous xenografts. Restoration of PTEN or knockdown of PIK3CB, but not PIK3CA, in glioblastoma cells markedly down-regulates the phosphorylation level of AKT, inhibits cell proliferation and colony formation, arrests the cell cycle at the G0/G1 stage, and promotes caspase-dependent apoptosis. Combined treatment with PTEN restoration and PIK3CB knockdown shows strong synergy. PTEN restoration or PIK3CB knockdown is also able to efficiently inhibit the growth of human U251 glioblastoma xenografts in nude mice, while tumor growth is entirely suppressed by a combination of the two treatments. In addition, we found that the mRNA levels of inhibitors of apoptosis proteins (IAPs) are reduced in U251 cells by PTEN restoration, suggesting that combined antitumor effects may also be partly attributed to the inhibition of the IAP pathway by PTEN restoration. Collectively, our results demonstrate that PI3 K isoforms play specific roles in tumorigenesis, and that combined treatment of PTEN restoration and PIK3CB siRNA is a promising gene therapy strategy for PTEN-deficient gliomas.

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Titel: PTEN restoration and PIK3CB knockdown synergistically suppress glioblastoma growth in vitro and in xenografts
verfasst von: Hongbo Chen
Lin Mei
Lanzhen Zhou
Xiaomeng Shen
Caiping Guo
Yi Zheng
Huijun Zhu
Yongqiang Zhu
Laiqiang Huang
Publikationsdatum: 01.08.2011
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2011
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-010-0492-2

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