Cyclooxygenase-2 in cancer cells and macrophages induces colon cancer cell growth by cigarette smoke extract.
Cigarette smoking, cyclooxygenase-2 (COX-2) and macrophages are independently associated with colorectal cancer. In the present study, cigarette smoke ethanol extract was applied to colon cancer cells (SW1116) or indirectly via activated macrophages (THP-1 cells) to attest their effects on cancer cell proliferation and tumor growth both in vitro and in vivo. Ethanol extract induced COX-2 expression in SW1116 and THP-1 cells. Combination of THP-1 pre-incubated medium and ethanol extract further potentiated COX-2 expression and proliferation of SW1116 cells. Tumor growth in nude mice was positively associated with the medium and/or ethanol extract treatments, together with the up-regulation of cell proliferation and angiogenesis, and down-regulation of apoptosis. Application of a COX-2 inhibitor (SC236) reduced tumor growth as well as cell proliferation and angiogenesis. These actions are partially depended on the decrease of COX-2 expression. Taken together, inhibition of COX-2 activity may have significant implication to prevent colon cancer in smokers.
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China.
Edgar S L
ES
Liu
Vivian Y
VY
Shin
Yi-Ni
YN
Ye
Jiing-Chyuan
JC
Luo
William K K
WK
Wu
Chi-Hin
CH
Cho
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D045424:Complex Mixtures / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D012906:Smoke; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014026:Nicotiana; D014316:Tritium; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000096926:Benzenesulfonamides
D045424:Complex Mixtures; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D000431:Ethanol; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D012906:Smoke; D013449:Sulfonamides; D013936:Thymidine; D014316:Tritium; D042461:Vascular Endothelial Growth Factor A; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human