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.
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