Suppression of 5-lipoxygenase gene is involved in triptolide-induced apoptosis in pancreatic tumor cell lines

Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The purpose of this study was to investigate the effects of triptolide (TL) on proliferation and apoptosis of pancreatic cancer cells in vitro. We found that TL induced prominent growth inhib...

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Vydané v:Biochimica et biophysica acta Ročník 1770; číslo 7; s. 1021 - 1027
Hlavní autori: Zhou, G.X., Ding, X.L., Huang, J.F., Zhang, H., Wu, S.B.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Netherlands Elsevier B.V 01.07.2007
Predmet:
5-lipoxygenase
Apoptosis - drug effects
Arachidonate 5-Lipoxygenase - metabolism
Bcl-2
Blotting, Western
Caspase 3 - metabolism
Caspase-3
Cell Line, Tumor
Cell Proliferation - drug effects
Diterpenes - pharmacology
DNA Primers
Enzyme-Linked Immunosorbent Assay
Epoxy Compounds - pharmacology
Flow Cytometry
Gene Expression Regulation - drug effects
Humans
In Situ Nick-End Labeling
Leukotriene B4 - metabolism
Luciferases
Pancreas - cytology
Pancreas - drug effects
Pancreatic tumor
Phenanthrenes - pharmacology
Proto-Oncogene Proteins c-bcl-2 - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Triptolide
Pancreatic tumor
Bcl-2
Triptolide
TL
LTB4
5-lipoxygenase
5-LOX
Caspase-3
ISSN:0304-4165, 0006-3002, 1872-8006
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Shrnutí:Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of response to conventional therapy. The purpose of this study was to investigate the effects of triptolide (TL) on proliferation and apoptosis of pancreatic cancer cells in vitro. We found that TL induced prominent growth inhibition and apoptosis in human pancreatic cell lines. In addition, TL treatment significantly down-regulated 5-lipoxygenase (5-LOX) expression, as well as downstream leukotriene B4 (LTB4) production, in these cell lines. Furthermore, overexpression of 5-LOX in SW1990 cell lines or exogenous LTB4 made them more resistant to TL-induced apoptosis, which was correlated with increased Bcl-2 expression. Taken together, these findings suggest that inhibition of the 5-LOX pathway of arachidonic acid metabolism is associated with the anti-proliferation activity of TL. We also provide evidence that TL has clinical therapeutic value for patients with pancreatic cancer.
Bibliografia:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0304-4165
0006-3002
1872-8006
DOI:10.1016/j.bbagen.2007.03.002