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Journal of Environmental Pathology, Toxicology and Oncology
インパクトファクター: 1.625 5年インパクトファクター: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN 印刷: 0731-8898
ISSN オンライン: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2019030130
pages 329-343

Celecoxib Targeted Therapy Attenuates Mouse Colon Carcinogenesis through Modulation of Expression Patterns of Cancer Stem Cells

Elsayed I. Salim
Tanta University, Faculty of Science, Zoology Department, Research Laboratory of Molecular Carcinogenesis, Tanta, 31527-Egypt
Magdy E. Mahfouz
Kafrelsheikh University, Faculty of Science, Department of Zoology, Kafrelsheikh-Egypt
Jin Seok Kang
Department of Biomedical Laboratory Science, Namseoul University, Seoul, South Korea
Mona M. Hegazi
Tanta University, Faculty of Science, Zoology Department, Research Laboratory of Molecular Carcinogenesis, Tanta, 31527-Egypt
Hager M. Helmy
Tanta University, Faculty of Science, Zoology Department, Research Laboratory of Molecular Carcinogenesis, Tanta, 31527-Egypt
Eman A. Eltonouby
Tanta University, Faculty of Science, Zoology Department, Research Laboratory of Molecular Carcinogenesis, Tanta, 31527-Egypt

要約

This study was designated to explore the role of cancer stem cells (CSCs) during chemically induced mouse colon carcinogenesis (by 1,2- dimethylhydrazine dihydrochloride, DMH) with/or without the treatment with a targeted (anti-COX-2) therapeutic drug, celecoxib. Two experiments were conducted. The first, a short-term, 16-week mouse colon carcinogenesis bioassay, demonstrates the early stages of colon carcinogenesis. The other is a medium-term, 32-week mouse colon cancer experiment that mimics an end point of colon malignancy. Colon tumors were detected in animals after 32 weeks; histopathologically, they varied from benign hyperplastic polyps and adenomas to dysplastic polyps, adenocarcinomas, and invasive carcinomas. The overall colon tumor incidences, multiplicities, and volumes were obviously reduced when treated with celecoxib after DMH initiation. The immunohistochemical (IHC) labeling indexes (L1%) of the proliferating cell nuclear antigen (PCNA) were lower in the colonic epithelium in both experiments after treatment with celecoxib. Also, the IHC expression patterns of CD133 and CD44, known to associate CSCs, showed differential changes depending on the end-point stage of carcinogenesis and celecoxib treatment. Moreover, the biochemical aldehyde dehydrogenase-1 (ALDH-1) activity levels, a known CSC marker in colonic epithelia, were downregulated after 16 weeks but were upregulated after 32 weeks. Flow cytometric analysis showed that numbers of CD133 cells increased in the colonic epithelia of mice after 16 weeks, while the numbers of CD44 but not CD133 cells increased after 32 weeks. Treatment with celecoxib after DMH induced significant increase in apoptotic cell numbers by 47% after 16 weeks, but these numbers had not changed after 32 weeks compared with the corresponding group treated DMH only. Thus, the specific markers and CSC populations targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. This drug could be useful during targeted therapy for colon cancer patients.

参考

  1. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913-21.

  2. Thomassen I, van Gestel YR, Lemmens VE, de Hingh IH. Incidence, prognosis, and treatment options for patients with synchronous peritoneal carcinomatosis and liver metastases from colorectal origin. Dis Colon Rectum. 2013;56(12):1373-80.

  3. Herzog CM, Dey S, Hablas A, Khaled HM, Seifeldin IA, Ramadan M, El-Hamzawy H, Wilson ML, Soliman AS. Geographic distribution of hematopoietic cancers in the Nile delta of Egypt. Annals Oncol. 2012;23(10):2748-55.

  4. Avgustinova A, Benitah SA. The epigenetics of tumour initiation: cancer stem cells and their chromatin. Curr Op Gen Development. 2016;36:8-15.

  5. Vaiopoulos AG, Kostakis ID, Koutsilieris M, Papavassiliou AG. Colorectal cancer stem cells. Stem Cells (Dayton, OH). 2012;30(3):363-71.

  6. Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 1997;90(12):5013-21.

  7. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997;90(12):5002-12.

  8. Tachezy M, Zander H, Gebauer F, Marx A, Kaifi JT, Izbicki JR, Bockhorn M. Activated leukocyte cell adhesion molecule (CD166)-its prognostic power for colorectal cancer patients. J Surg Res. 2012;177(1):e15-20.

  9. Han Z, Chen Z, Zheng R, Cheng Z, Gong X, Wang D. Clinicopathological significance of CD133 and CD44 expression in infiltrating ductal carcinoma and their relation-ship to angiogenesis. World J Surg Oncol. 2015;13(1):1-8.

  10. Ferrandina G, Lauriola L, Distefano MG, Zannoni GF, Gessi M, Legge F, Maggiano N, Mancuso S, Capelli A, Scambia G, Ranelletti FO. Increased cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients. J Clin Oncol. 2002;20(4):973-81.

  11. Chute JP, Muramoto GG, Whitesides J, Colvin M, Safi R, Chao NJ, McDonnell DP. Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci. 2006;103(31):11707-12.

  12. Shao C, Sullivan JP, Girard L, Augustyn A, Yenerall P, Rodriguez-Canales J, Liu H, Behrens C, Shay JW, Wistuba II, Minna JD. Essential role of aldehyde dehydrogenase 1a3 for the maintenance of non-small cell lung cancer stem cells is associated with the STAT3 pathway. Clin Cancer Res. 2014;20(15):4154-66.

  13. Bhat PV, Samaha H. Kinetic properties of the human liver cytosolic aldehyde dehydrogenase for retinal isomers. Biochem Pharmacol. 1999;57(2):195-97.

  14. Mortaz E, Gudarzi H, Tabarsi P, Adcock IM, Masjedi MR, Jamaati HR, Garssen J, Velayati AA, Redegeld FA. Flow cytometry applications in the study of immunological lung disorders. Iranian J Allergy Asthma Immunol. 2015;14(1):12-18.

  15. Vinothkumar R, Vinoth Kumar R, Sudha M, Viswanathan P, Balasubramanian T, Nalini N. Modulatory effect of troxerutin on biotransforming enzymes and preneoplasic lesions induced by 1,2-dimethylhydrazine in rat colon car-cinogenesis. Exper Mol Pathol. 2014;96(1):15-26.

  16. Wormser U, Langenbach R, Peddada S, Sintov A, Brodsky B, Nyska A. Reduced sulfur mustard-induced skin toxicity in cyclooxygenase-2 knockout and celecoxib-treated mice. Toxicol Appl Pharmacol. 2004;200(1):40-47.

  17. Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother. 2010;1(2):87-93.

  18. Turosov V, Mohr U, editors. Pathology of tumours in laboratory animals. Vol. 2: Tumours of the mouse. Lyon, France: International Agency for Research on Cancer (IARC; WHO); 1990.

  19. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29(4):577-80.

  20. Zaritskaya L, Shafer-Weaver KA, Gregory MK, Strobl SL, Baseler M, Malyguine A. Application of a flow cytometric cytotoxicity assay for monitoring cancer vaccine trials. J Immunother (Hagerstown, MD: 1997). 2009;32(2):186-94.

  21. Dean PN, Jett JH. Mathematical analysis of DNA distri-butions derived from flow microfluorometry. J Cell Biol. 1974;60(2):523-27.

  22. Vindelev LL. Flow microfluorometric analysis of nuclear DNA in cells from solid tumors and cell suspensions. Virchows Archiv B. 1977;24(1):227-42.

  23. Spyratos F. DNA content and cell cycle analysis by flow cytometry in clinical samples: application in breast cancer. Bio Cell. 1993;78(1-2):69-72.

  24. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457(7229):608-11.

  25. Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annual Rev Med. 2007;58:267-84.

  26. Salim EI, Hegazi MM, Kang JS, Helmy HM. Expression patterns of cancer stem cell markers during specific celecoxib therapy in multistep rat colon carcinogenesis bioas-says. Asian Pac J Cancer Prevent. 2016;17(3):1023-35.

  27. O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106-10.

  28. Keysar SB, Jimeno A. More than markers: biological significance of cancer stem cell-defining molecules. Mol Cancer Therap. 2010;9(9):2450-7.

  29. Nagata T, Sakakura C, Komiyama S, Miyashita A, Nishio M, Murayama Y, Komatsu S, Shiozaki A, Kuriu Y, Ikoma H, Nakanishi M, Ichikawa D, Fujiwara H, Okamoto K, Ochiai T, Kokuba Y, Sonoyama T, Otsuji E. Expression of cancer stem cell markers CD133 and CD44 in lo- coregional recurrence of rectal cancer. Anticancer Res. 2011;31(2):495-500.

  30. Fhu CW, Graham AM, Yap CT, Al-Salam S, Castella A, Chong SM, Lim YC. Reed-Sternberg cell-derived lymphotoxin-a activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma. Blood. 2014;124(19):2973-82.

  31. Mieog JS, de Kruijf EM, Bastiaannet E, Kuppen PJ, Sajet A, de Craen AJ, Smit VT, van de Velde CJ, Liefers GJ. Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer. BMC Cancer. 2012;12:42.

  32. Moreb JS. Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther. 2008;3(4):237-46.

  33. Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69(8):3382-89.

  34. Hamoya T, Fujii G, Miyamoto S, Takahashi M, Totsuka Y, Wakabayashi K, Toshima J, Mutoh M. Effects of NSAIDs on the risk factors of colorectal cancer: a mini review. Genes Environ. 2016;38.

  35. Deng Y, Su Q, Mo J, Fu X, Zhang Y, Lin EH. Celecoxib downregulates CD133 expression through inhibition of the Wnt signaling pathway in colon cancer cells. Cancer Investig. 2013;31(2):97-102.

  36. Duncan K, Uwimpuhwe H, Czibere A, Sarkar D, Libermann TA, Fisher PB, Zerbini LF. NSAIDs induce apoptosis in nonproliferating ovarian cancer cells and inhibit tumor growth in vivo. IUBMB Life. 2012;64(7):636-43.

  37. Saini MK, Sanyal SN. PTEN regulates apoptotic cell death through PI3-K/Akt/GSK3p signaling pathway in DMH induced early colon carcinogenesis in rat. Exper Mol Pathol. 2012;93(1):135-46.


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