Downregulation of PIK3CB by siRNA suppresses malignant glioma cell growth in vitro and in vivo.
EGFR overexpression is the most frequent and important molecular event in the development of astrocytic gliomas, and the P13K signaling pathway is one of the most important downstream pathways of EGFR. EGFR and other members of the receptor tyrosine kinases (RTKs) family, such as VEGFR, PDGFR, and IGFR, et cetera, are often overexpressed in most of malignant gliomas and share common downstream signaling pathways. Therefore, it is considered that directly targeting the downstream PI3K pathway may be more effective in blocking multiple inputs. The PIK3CB gene encoding the class 1A PI3K catalytic subunit p110beta was selected as the target of therapeutic approach for malignant gliomas in the present study. Human U251 glioblastoma cells with high endogenous p110beta expression were transfected with plasmid-based siRNA targeting PIK3CB gene. It was found that downregulation of p110beta expression resulted in the suppression of cell proliferation, arrest of cell cycle, reduction of cell invasion, and promotion of cell apoptosis in vitro. In addition, the growth of the subcutaneous U251 glioma in the nude mice treated with siRNA targeting PIK3CB was significantly inhibited. These results demonstrate that PIK3CB overexpression may play an oncogenic role in the PI3K pathway, and the plasmid-based siRNA targeting of PIK3CB is a potential and promising approach for the treatment of malignant gliomas.
Pu
Peiyu
P
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, People's Republic of China. pupeiyu33@hotmail.com
Kang
Chunsheng
C
Zhang
Zhiyong
Z
Liu
Xiaozhi
X
Jiang
Hao
H
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases