Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.
The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.
Hwang
S-K
SK
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Jin
H
H
Kwon
J T
JT
Chang
S-H
SH
Kim
T H
TH
Cho
C-S
CS
Lee
K H
KH
Young
M R
MR
Colburn
N H
NH
Beck
G R
GR
Yang
H-S
HS
Cho
M-H
MH
D000336:Aerosols; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D023421:Models, Animal; D011094:Polyethyleneimine; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014162:Transfection / Q000379:methods
D000336:Aerosols; D051017:Apoptosis Regulatory Proteins; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins; D018808:Transcription Factor AP-1; D011094:Polyethyleneimine; D008156:Luciferases