Creation of an apoptin-derived peptide that interacts with SH3 domains and inhibits glioma cell migration and invasion.
Glioblastoma multiforme (GBM) is an aggressive tumor of the central nervous system characterized by high rates of recurrence, morbidity, and mortality. This study investigated the antitumor effects of an apoptin-derived peptide (ADP) on glioma cells and explored the underlying mechanisms. The U251, U87, and C6 glioma cell lines were used in the present study, and the expression of p-Akt, Akt, and MMP-9 was determined through Western blotting, quantitative real-time PCR, and hematoxylin and eosin (HE) staining. Tumor growth was evaluated by magnetic resonance imaging, and cell viability was assessed through an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay. Glioma cell metastasis was evaluated using transwell migration, invasion, and scratch-wound assays. An ADP was designed and synthesized based on the results of a domain-based analysis of the structure of apoptin. The ADP inhibited glioma cell viability, invasion and migration, and treatment with the synthesized ADP led to downregulation of p-Akt and MMP-9 and inhibited MMP-9 translation. The ADP also inhibited glioma invasion and migration in vivo, and HE staining showed decreases in the satellite-like invasion of cell masses and apoptotic cell populations after treatment with the ADP. Our findings demonstrate that treatment with an ADP can suppress glioma cell migration and invasion via the PI3K/Akt/MMP-9 signaling pathway and provide a new platform for the development of drugs for treating glioma.
Department of Pharmacology, Harbin Medical University, Harbin, People's Republic of China.
Weiwei
W
Song
Daqing Oilfield General Hospital, Daqing, People's Republic of China.
Hengyu
H
Zhao
Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, People's Republic of China.
Zhongqi
Z
Cui
Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, People's Republic of China.
Xiaoyu
X
Ma
Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, People's Republic of China.
Wenwen
W
Zhang
Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, People's Republic of China.
Di
D
Wang
Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, People's Republic of China.
Anqi
A
Liu
Department of Pharmacology, Harbin Medical University, Harbin, People's Republic of China. yuanlijie1225@163.com.|Department of Biochemistry and Molecular Biology, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, 163319, People's Republic of China. yuanlijie1225@163.com.
Lijie
L
Yuan
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D036022:Capsid Proteins / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D018909:src Homology Domains / Q000502:physiology*
D036022:Capsid Proteins; D020780:Matrix Metalloproteinase 9; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; C091717:VP3 protein, Chicken anemia virus
Akt; Apoptin-derived peptide; Glioma cells; PI3K
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