Restoration of leukotriene B(4)-12-hydroxydehydrogenase/15- oxo-prostaglandin 13-reductase (LTBDH/PGR) expression inhibits lung cancer growth in vitro and in vivo.
Leukotriene B(4)-12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase (LTBDH/PGR) is a bifunctional enzyme capable of inactivating leukotriene B(4) (LTB(4)) and 15-oxo-prostaglandins (15-PGs). Its role in growth suppressive functions in lung cancer was studied in in vitro and in vivo systems. The LTBDH/PGR gene was expressed in lung cancer cell lines through recombinant adenovirus infection, and through a tetracycline-inducible expression system. After restoration of LTBDH/PGR expression in LTBDH/PGR-negative (H1299) or -low (A549) lung cancer cell lines, the restored enzyme induced apoptosis and growth inhibition in vitro. Ectopic expression of LTBDH/PGR caused also suppression of tumorigenicity of A549 cells in nude mice. In contrast, LTBDH/PGR over-expression in LTBDH/PGR-positive (H157) lung cancer cell line induced little apoptosis and growth inhibition. This study indicates that restoration of LTBDH/PGR expression is effective in preventing lung cancer growth in vitro and in vivo.
Zhao
Yuhua
Y
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, United States.
Weng
Chu-Chun
CC
Tong
Min
M
Wei
Jingyan
J
Tai
Hsin-Hsiung
HH
D011452:15-Oxoprostaglandin 13-Reductase / Q000235:genetics / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019076:Transgenes / Q000235:genetics; D047368:Tumor Burden / Q000235:genetics
D000429:Alcohol Oxidoreductases; C082646:leukotriene B4 12-hydroxydehydrogenase; D011452:15-Oxoprostaglandin 13-Reductase