Reduced 15S-lipoxygenase-2 expression in esophageal cancer specimens and cells and upregulation in vitro by the cyclooxygenase-2 inhibitor, NS398

Neoplasia. Mar-Apr 2003;5(2):121-7. doi: 10.1016/s1476-5586(03)80003-9.

Abstract

Alterations in arachidonic acid metabolism are involved in human carcinogenesis. Cyclooxygenase (COX) and lipoxygenase (LOX) are key enzymes in this metabolism. We analyzed the expression of 15S-lipoxygenase-2 (15-LOX-2) mRNA and protein in surgical specimens from normal (N=37) and malignant (63) esophageal tissues using in situ hybridization and immunohistochemistry (IHC), and in normal (1), premalignant (1), and malignant (5) esophageal cell lines using Northern and Western blotting. 15-LOX-2 was expressed in normal esophageal epithelial cells (EECs) at the highest levels, whereas an SV40-immortalized HET-1A line and three of five esophageal cancer cell lines failed to express it at detectable levels. 15-LOX-2 was detected in 76% (28/37) of the normal esophageal mucosae, but only in 46% (29/63) of the cancer specimens using IHC (P<.01). Transient transfection of 15-LOX-2 expression vectors into esophageal cancer cells significantly inhibited the proliferation of 15-LOX-2-negative cancer cells. The COX-2 inhibitor, NS398, induced 15-LOX-2 expression in esophageal cancer cells, which is associated with reduced cell viability. This study demonstrated that 15-LOX-2 expression is lost in esophageal cancers and that the induction of 15-LOX-2 can inhibit cancer cell proliferation. Further investigation of the effects of nonsteroidal anti-inflammatory drugs on 15-LOX-2 expression and apoptosis in esophageal cancer cells may be warranted.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Arachidonate 15-Lipoxygenase / biosynthesis*
  • Arachidonate 15-Lipoxygenase / genetics*
  • Blotting, Northern
  • Blotting, Western
  • Bromodeoxyuridine / pharmacology
  • Cell Division
  • Cell Line, Tumor
  • Cell Survival
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / genetics*
  • Humans
  • Immunohistochemistry
  • Microscopy, Fluorescence
  • Mucous Membrane / pathology
  • Nitrobenzenes / pharmacology*
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology*
  • Transfection
  • Up-Regulation*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Nitrobenzenes
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • RNA
  • ALOX15B protein, human
  • Arachidonate 15-Lipoxygenase
  • Bromodeoxyuridine