Effects of Celecoxib on Cycle Kinetics of Gastric Cancer Cells and Protein Expression of Cytochrome C and Caspase-9

  • Wang, Yu-Jie (Department of Gastroenterology, Zhengzhou People's Hospital Affiliated to Southern Medical University) ;
  • Niu, Xiao-Ping (Department of Digestion Medicine, Yijishan Hospital of Wannan Medicine College) ;
  • Yang, Li (Department of Gastroenterology, Zhengzhou People's Hospital Affiliated to Southern Medical University) ;
  • Han, Zhen (Department of Digestion Medicine, Yijishan Hospital of Wannan Medicine College) ;
  • Ma, Ying-Jie (Department of Gastroenterology, Zhengzhou People's Hospital Affiliated to Southern Medical University)
  • Published : 2013.04.30


Objective: This investigation aimed to determine effects of celecoxib on the cell cycle kinetics of the gastric cancer cell line MGC803 and the mechanisms involved by assessing expression of cytochrome C and caspase-9 at the protein level. Methods: Cell proliferation of MGC803 was determined by MTT assay after treatment with celecoxib. Apoptosis was assessed using fluorescence staining and cell cycle kinetics by flow cytometry. Western blotting was used to detect the expression of caspase-9 protein and of cytochrome C protein in cell cytosol and mitochondria. Results: Celecoxib was able to restrain proliferation and induce apoptosis in a dose- and time-dependent manner, inducing G0/G1 cell cycle arrest, release of cytochrome C into the cytosol, and cleavage of pro-caspase-9 into its active form. Conclusion: Celecoxib can induce apoptosis in MGC803 cells through a mechanism involving cell cycle arrest, mitochondrial cytochrome C release and caspase activation.


Supported by : Natural Science Foundation


  1. Arber N (2008). Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point. Cancer Epidemiol Biomarkers Prev, 17, 1852-7.
  2. Barr H (2011). Gastrointestinal cancer: current screening strategies. Recent Results Cancer Res, 185, 149-57.
  3. Bazuro GE, Torino F, Gasparini G, Capurso L (2008). Chemoprevention in gastrointestinal adenocarcinoma: for few but not for all? Minerva Gastroenterol Dietol, 54, 429-44.
  4. Calviello G, Di Nicuolo F, Piccioni E, et al (2003). gamma-Tocopheryl quinone induces apoptosis in cancer cells via caspase-9 activation and cytochrome c release. Carcinogenesis, 24, 427-33.
  5. Chakraborti AK, Garg SK, Kumar R, Motiwala HF, Jadhavar PS (2010). Progress in COX-2 inhibitors: a journey so far. Curr Med Chem, 17, 1563-93.
  6. Chen WT, Hung WC, Kang WY, et al (2009). Overexpression of cyclooxygenase-2 in urothelial carcinoma in conjunction with tumor-associated-macrophage infiltration, hypoxiainducible factor-1alpha expression, and tumor angiogenesis. APMIS, 117, 176-84.
  7. Clemett D, Goa KL (2000). Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain. Drugs, 59, 957-80.
  8. Coussens LM, Werb Z (2002). Inflammation and cancer. Nature, 420, 860-7.
  9. Entezari Heravi R, Hadizadeh F, Sankian M, et al (2011). Novel selective Cox-2 inhibitors induce apoptosis in Caco-2 colorectal carcinoma cell line. Eur J Pharm Sci, 44, 479-86.
  10. Fischer SM, Hawk ET, Lubet RA (2011). Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention. Cancer Prev Res, 4, 1728-35.
  11. Fisher JC, Gander JW, Haley MJ, et al (2011). Inhibition of cyclooxygenase 2 reduces tumor metastasis and inflammatory signaling during blockade of vascular endothelial growth factor. Vasc Cell, 3, 22.
  12. Fujimura T, Ohta T, Oyama K, Miyashita T, Miwa K (2007). Cyclooxygenase-2 (COX-2) in carcinogenesis and selective COX-2 inhibitors for chemoprevention in gastrointestinal cancers. J Gastrointest Cancer, 38, 78-82.
  13. Ghosh N, Chaki R, Mandal V, Mandal SC (2010). COX-2 as a target for cancer chemotherapy. Pharmacol Rep, 62, 233-44.
  14. Gu Q, Wang JD, Xia HH, et al (2005). Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in gastric cancer. Carcinogenesis, 26, 541-6.
  15. Hsu YL, Kuo YC, Kuo PL, et al (2005). Apoptotic effects of extract from Antrodia camphorata fruiting bodies in human hepatocellular carcinoma cell lines. Cancer Lett, 221, 77-89.
  16. Khan Z, Khan N, Tiwari RP, et al (2011). Biology of Cox-2: an application in cancer therapeutics. Curr Drug Targets, 12, 1082-93.
  17. Lai MY, Huang JA, Liang ZH, et al (2004). Cyclooxygenase-2 expression: a significant prognostic indicator for patients with colorectal cancer. Clin Cancer Res, 10, 8465-71.
  18. Li S, Tong Q, Zhang W, et al (2008). Mechanism of growth inhibitory effects of cyclooxygenase-2 inhibitor-NS398 on cancer cells. Cancer Invest, 26, 333-7.
  19. Liu H, Xiao J, Yang Y, et al (2011). COX-2 expression is correlated with VEGF-C, lymphangiogenesis and lymph node metastasis in human cervical cancer. Microvasc Res, 82, 131-40.
  20. Liou JP, Hsu KS, Kuo CC, Chang CY, Chang JY (2007). A novel oral indoline-sulfonamide agent, N-[1-(4-methoxybenzenesulfonyl)-2, 3-dihydro-1H-indol-7-yl] -isonicotinamide (J30), exhibits potent activity against human cancer cells in vitro and in vivo through the disruption of microtubule. J Pharmacol Exp Ther, 323, 398-405.
  21. Matthias C, Schuster MT, Zieger S, Harreus U (2006). COX-2 inhibitors celecoxib and rofecoxib prevent oxidative DNA fragmentation. Anticancer Res, 26, 2003-7.
  22. Mehar A, Macanas-Pirard P, Mizokami A, et al (2008). The effects of cyclooxygenase-2 expression in prostate cancer cells: modulation of response to cytotoxic agents. J Pharmacol Exp Ther, 324, 1181-7.
  23. Ogunwobi OO, Liu C (2011). Hepatocyte growth factor upregulation promotes carcinogenesis and epithelialmesenchymal transition in hepatocellular carcinoma via Akt and COX-2 pathways. Clin Exp Metastasis, 28, 721-31.
  24. Ohno Y, Ohno S, Suzuki N, et al (2005). Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma. Int J Cancer, 114, 696-701.
  25. Park SW, Kim HS, Hah JW, et al (2010). Celecoxib inhibits cell proliferation through the activation of ERK and p38 MAPK in head and neck squamous cell carcinoma cell lines. Anticancer Drugs, 21, 823-30.
  26. Pietenpol JA, Stewart ZA (2002). Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis. Toxicology, 181-182, 475-81.
  27. Smith WL, DeWitt DL, Garavito RM (2000). Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem, 69, 145-82.
  28. Sobolewski C, Cerella C, Dicato M, Diederich M (2011). Cox-2 inhibitors induce early c-Myc downregulation and lead to expression of differentiation markers in leukemia cells. Cell Cycle, 10, 2978-93.
  29. Thiel A, Mrena J, Ristimaki A (2011). Cyclooxygenase-2 and gastric cancer. Cancer Metastasis Rev, 30, 387-95.
  30. Wang GY, Zhang JW, Lu QH, Xu RZ, Dong QH (2007). Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in mitochondrial transmembrane potential and caspase activation. J Zhejiang Univ Sci B, 8, 248-55.
  31. Wu K, Nie Y, Guo C, et al (2009). Molecular basis of therapeutic approaches to gastric cancer. J Gastroenterol Hepatol, 24, 37-41.
  32. Xiao H, Zhang Q, Lin Y, Reddy BS, Yang CS (2008). Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells. Int J Cancer, 122, 2115-24.
  33. Zhang CL, Wu LJ, Tashiro S, Onodera S, Ikejima T (2004). Oridonin induced A375-S2 cell apoptosis via bax-regulated caspase pathway activation, dependent on the cytochrome c/caspase-9 apoptosome. J Asian Nat Prod Res, 6, 127-38.

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