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COX-2 INHIBITOR INDUCED APOPTOSIS IN ORAL SQUAMOUS CELL CARCINOMA CELL LINE THROUGH AKT PATHWAY  

Seo, Young-Ho (Dept. of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University)
Han, Se-Jin (Dept. of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University)
Lee, Jae-Hoon (Dept. of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University)
Publication Information
Maxillofacial Plastic and Reconstructive Surgery / v.30, no.1, 2008 , pp. 30-40 More about this Journal
Abstract
The objectives of this study was to check up the effect of celecoxib, COX-2 inhibitor, on the pathogenesis of oral squamous cell carcinoma. After mefenamic acid, aspirin and celecoxib, COX-2 inhibitor, were inoculated to HN 22 cell line, the following results were obtained through tumor cell viability by wortmannin, growth curve of tumor cell line, apoptotic index, PGE2 synthesis, total RNA extraction, RT-PCR analysis and TEM features. 1. When wortmannin and celecoxib were given together, the survival rate of tumor cells was lowest about 47 %. So wortmannin had an effect on the decrease of survival rate of tumor cells. 2. In growth curve, the slowest growth was observed in celecoxib inoculated group. 3. The synthesis of PGE2 was decreased in all group and the obvious suppression and highest apoptotic index was observed in celecoxib inoculated group. 4. Suppression of expression of COX-2 mRNA was evident in celecoxib inoculated group. But that of COX-1,2 mRNA was observed in mefenamic acid inoculated group and aspirin inoculated group. 5. In celecoxib inoculated group, mRNA expression of AKT1 was decreased and that of PTEN & expression of caspase 3 and 9 was evidently increased. Depending on above results, when celecoxib was inoculated to oral squamous cell carcinoma cell line, an increase of mRNA expression of caspase 3,9 and PTEN is related to a decrease of mRNA expression of AKT1. Wortmannin had an effect on the decrease of survival rate of tumor cells. Celecoxib might induce apoptosis of tumor cell by suppression of AKT1 pathway and COX-2 inhibition. This results suggested that COX-2 inhibitor might be significantly effective in chemoprevention of oral squamous cell carcinoma.
Keywords
COX-2 growth inhibitor; Apoptosis of oral squamous cell carcinoma;
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1 Williams CW, DuBois RN : Prostaglandin endoperoxide synthase : why two isoforms? Am J Physiol 270 : G393, 1996
2 Oshima M, Dinchuk JE, Kargman SL et al : Suppression of intestinal polyposis in Apc$\Delta$716 knockout mice by inhibition of cyclooxygenase 2(COX-2). Cell 87 : 803, 1996   DOI   ScienceOn
3 Chan G, Boyle JO, Yang EK et al : Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res 59 : 991, 1999   PUBMED
4 Watanabe H, Saito H, Rychahou PG et al : Aging is associated with decreased pancreatic acinar cell regeneration and phosphatidylinositol 3-kinase/Akt activation. Gastroenterology 128(5) : 1391, 2005   DOI   ScienceOn
5 Neri LM, Borgatti P, Tazzari PL et al : The phosphoinositide 3-kinase/Akt1 pathway involvement in drug and alltrans-retinoic acid resistance of leukemia cells. Mol Cancer Res 1(3) : 234, 2003   PUBMED
6 Wieder T, Essmann F, Prokop A et al : Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3. Blood 97(5) : 1378, 2001   DOI   ScienceOn
7 Barnes NL, Warnberg F, Farnie G et al : Cyclooxygenase-2 inhibition : effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer. Br J Cancer 96(4) : 575, 2007   DOI   ScienceOn
8 Bock JM, Menon SG, Sinclair LL et al : Celecoxib toxicity is cell cycle phase specific. Cancer Res 67(8) : 3801, 2007   DOI   ScienceOn
9 Trifan OC, Smith Rm, Thompson BD et al : Overexpression of cyclooxygenase-2 induces cell cycle arrest. Evidence for a prostaglandin-independent mechanism. J Biol Chem 274(48) : 34141, 1999   DOI   PUBMED
10 Mattia C, Coluzzi F : COX-2 inhibitors : pharmacological data and adverse effects. Minerva Anestesiol 71(7-8) : 461, 2005   PUBMED
11 Chen LC, Ashcroft DM : Risk of myocardial infarction associated with selective COX-2 inhibitors : Meta-analysis of randomised controlled trials. Pharmacoepidermiol Drug Saf Apr, 2007
12 Waddell WR, Ganser GF, Cerise EJ et al : Sulindac for polyposis of the colon. Am J Surg 157 : 175, 1989   DOI   ScienceOn
13 Masferrer JL, Zweifel BS, Manning PT et al : Selective inhibition of inducible cyclooxygenase-2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci USA 91(8) : 3228, 1994
14 Susin SA, Lorenza HK, Zamzami N et al : Molecular chacterization of mitochondrial apoptosis-inducing factor. Nature 397 : 441, 1999   DOI   ScienceOn
15 Ding H, Han C, Zhu J et al : Celecoxib derivatives induce apoptosis via the disruption of mitochondrial membrane potential and activation of caspase 9. Int J Cancer 113(5) : 803, 2005   DOI   ScienceOn
16 Baek JY, Hur W, Wang JS et al : Selective COX-2 inhibitor, NS-398, suppresses cellular proliferation in human hepatocellular carcinoma cell lines via cell cycle arrest. World J Gastroenterol 13(8) : 1175, 2007   DOI   PUBMED
17 Crompton MB : Bid and the permeabilization of mitochondrial outer membrane in apoptosis. Curr Opin Cell Biol 12(4) : 414, 2000   DOI   ScienceOn
18 Gilroy DW, Saunders MA, Wu KK : COX-2 expression and cell cycle progression in human fibroblasts. Am J Physiol Cell Physiol 281(1) : C188, 2001   DOI
19 Toyoshima T, Kamijo R, Ito D et al : Inhibitor of cyclooxygenase-2 induces cell-cycle arrest in the epithelial cancer cell line via up-regulation of cyclin dependent kinase inhibitor p21. Br. J Cancer 86(7) : 1150, 2002   DOI   ScienceOn
20 Hsu Al, Ching TT, Wang DS et al : The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 275(15) : 11397, 2000   DOI   ScienceOn
21 Krammer PH, Behnnann I, Daniel P et al : Regulation of apoptosis in the immune system. Curr Biol 6 : 279, 1994   DOI   ScienceOn
22 Smalley WE, DuBois RN : Colorectal cancer and nonsteroidal anti-inflammatory drugs. Adv Pharmacol 39 : 1, 1997   DOI
23 Vazquez F, Sellers WR : The PTEN tumor suppressor protein: an antagonist of phosphoinositide 3-kinase signalling. Biochem Biophys Acta 1470 : M21-M35, 2000
24 Kawamori T, Rao CV, Seibert K et al : Chemopreventive activity of Celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 58 : 409, 1998   PUBMED
25 Park C, Kim GY, Kim GD et al : Induction of G2/M arrest and inhibition of cyclooxygenase-2 activity by curcumin in human bladder cancer T24 cells. Oncol Rep 15(5) : 1225, 2006   PUBMED
26 Brown JR, DuBois RN : COX-2 : A molecular target for colorectal cancer prevention. J Clin Oncol 23 : 2840, 2005   DOI   ScienceOn
27 Li H, Zhu H, Xu C, et al : Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94(4) : 491, 1998   DOI   ScienceOn
28 Pyrko P, kardosh A, Liu YT et al : Calcium-activated endoplasmic reticulum stress as a major component of tumor cell death induced by 2,5-dimethyl-celecoxib, a noncoxib analogue of celecoxib. Mol Cancer Ther 6(4) : 1262, 2007   DOI   ScienceOn
29 Cheng JQ, Jiang X, Fraser M et al : Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian cancer : possible involvement of the phosphoinositide-3 kinase/Akt pathway. Drug Resist Updat 5(3-4) : 131-46, 2002   DOI   ScienceOn
30 Kaufmann SH, Earnshaw WC : Induction of apoptosis by cancer chemotherapy. Exp Cell Res 256(1) : 42, 2000   DOI   ScienceOn
31 Dvory SH, Cohen NE, Kazanov D et al : Celecoxib leads to G2/M arrest by induction of p21 and down-regulation of cyclin B1 expression in a p53-independent manner. Eur J Cancer 42(3) : 422, 2006   DOI   ScienceOn
32 Simon LS : Actions and toxicity of nonsteroidal antiinflammatory drugs. Curr Opin Rheum 8 : 169, 1996   DOI   ScienceOn
33 Paez J, Sellers WR : The PI3K/PTEN/Akt pathway : A critical mediator of oncogenic signaling. Cancer Treat Res 115 : 145, 2003   PUBMED
34 Lev-Aris S, Kazanov D, Liberman E et al : Down-regulation of $PGE_2$ by physiologic levels of celecoxib is not sufficient to induce apoptosis or inhibit cell proliferation in human colon carcinoma cell lines. Dig Dis Sci 52(4) : 1128, 2007   DOI
35 Germain ME, Gagnon V, Mathieu I et al : Akt regulates COX-2 mRNA and protein expression in mutated-PTEN human endometrial cancer cells. Int J Oncol 24(5) : 1311, 2004   PUBMED
36 Forastiere A, Koch W, Trotti A et al : Head and neck cancer. N Engl J Med 345 : 1890, 2001   DOI   ScienceOn
37 Amir K, Agarwal HK : Role of COX-2 selective inhibitors for prevention and treatment of cancer. Pharmazie 60(8) : 563, 2005   PUBMED
38 Sooriakumaran P : COX-2 inhibitors and the heart: are all coxibs the same? Postgrad Med J 82(966) : 242, 2006   DOI   ScienceOn
39 Sawaoka H, Tsuji S, Tsujii M et al : Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest 79(12) : 1469, 1999
40 Park JS, Jun HJ, et al : Radiosensitivity enhancement by combined treatment of celecoxib and gefitinib on human lung cancer cells. Clin Cancer Res 12(16) : 4989, 2006   DOI   ScienceOn