PYRIN domain of NALP2 inhibits cell proliferation and tumor growth of human glioblastoma.
NACHT leucine-rich domain and pyrin-containing protein 2 (NALP2) plays a crucial role in inflammation through regulation of NF-kappaB activity. The N-terminal PRYIN domain of NALP2 (PYD) functions similarly in inhibiting NF-kappaB activity. To investigate if NALP2 or PYD regulates cell proliferation or tumor growth of glioblastoma, lentiviruses carrying PYD (Lenti-PYD-Flag) was successfully packaged. Lenti-PYD-Flag is able to transduce tumor cells with high efficiency and mediate high expression of peptide PYD-Flag. Transduction with Lenti-PYD-Flag significantly inhibited cell proliferation and tumor growth of U-87 MG, but not other cell lines tested. PYD inhibited nuclear accumulation of endogenous p65. These findings imply that: (i) our pRRL-based lentiviral system can transduce tumor cells with high transduction efficiency, and mediate high level expression of, at least 1.8 kb, foreign genes; (ii) PYD inhibits cell proliferation and tumor growth of glioblastoma possibly through the inhibition of NF-kappaB activity, and PYD appears to be a promising candidate for the development of targeted therapy for glioblastoma.
Wu
Guo-Qing
GQ
Department of Oncology, Zhejiang Provincial People's Hospital, Hangzhou, China.
Liao
Yi-Ji
YJ
Qin
Zhi-Quan
ZQ
He
Li-Ru
LR
Chen
Yang-Chao
YC
Zeng
Yi-Xin
YX
Kung
Hsiang-Fu
HF
Xie
Dan
D
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D009361:Neoplasm Invasiveness; D010957:Plasmids / Q000235:genetics; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D051996:Transcription Factor RelA / Q000378:metabolism; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D048868:Adaptor Proteins, Signal Transducing; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha