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Journal of Cancer Research and Clinical Oncology

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01.07.2015 | Original Article – Cancer Research

Anti-LeY antibody enhances therapeutic efficacy of celecoxib against gastric cancer by downregulation of MAPKs/COX-2 signaling pathway: correlation with clinical study

verfasst von: Faisal Aziz, Xuesong Yang, Xiaoqi Wang, Qiu Yan

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2015

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Abstract

Introduction

Helicobacter pylori (H. pylori) is a major causative agent for the induction of chronic gastritis, gastric ulcer and gastric cancer. Celecoxib (COX-2 inhibitor) inhibits gastric cancer cell proliferation, but with low treatment efficacy, limiting its applications. It is important to develop a better strategy to improve the efficacy of celecoxib. Lewis Y (LeY) is a difucosylated oligosaccharide, highly expressed in 60–90 % of human epithelial cancers, including gastric cancer. We previously found that H. pylori infection was associated with high level of LeY in gastric cancer.

Material and Methods

Herein, we analyzed the correlation between H. pylori and cyclo-oxygenase-2 (COX-2), LeY, gastric markers (CA724 and GRN) in gastric patient’s tissue and serum samples by IHC and ELISA. Furthermore, we treated the primary gastric cancer cells with celecoxib, anti-LeY antibody or the combination, and analyzed their therapeutic efficacy on CA724, GRN and COX-2 expression by Western blot, flow cytometry and ELISA.

Results

We found that gastric cancer had significantly high expression of H. pylori, COX-2, CA724, and GRN compared to gastric ulcers and chronic gastritis (P < 0.0001). H. pylori level showed significant correlation with COX-2 (R—0.552), LeY (R—0.861), CA724 (R—0.714) and GRN (R—0.664) (P < 0.0001). Additionally, the combination therapy led to impressive inhibition of gastric cancer cell proliferation, with decreased expression of COX-2, CA724 and GRN through downregulation of MAPKs/COX-2 pathway (P < 0.01).

Conclusions

Our findings suggest that anti-LeY antibody enhances the cancer cell proliferation inhibitory effects of celecoxib, which might be a new feasible way for gastric cancer therapy.

Aziz F, Yang X, Wang X, Qiu Y (2013) Helicobacter pylori infection leads to gastric cancer with the coexpression of Lewis Y and CA724. Glycoconj J 30:411 (abstract)

Aziz F, Sherwani SK, Akhtar SS, Kazmi SU (2014a) Development of an in-house enzyme linked immunosorbent assay based on surface whole cell antigen for diagnosis of Helicobacter pylori infection in patients with gastroduodenal ulcer disease. World J Microbiol Biotechnol 30(1):305–315CrossRefPubMed

Aziz F, Yang X, Qingping W, Qiu Y (2014b) A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissue. Mol Med Rep [Epub ahead of print]

Cheng J, Fan XM (2013) Role of cyclooxygenase-2 in gastric cancer development and progression. World J Gastroenterol 19(42):7361–7368CrossRefPubMedCentralPubMed

Clarke K, Lee FT, Brechbiel MW, Smyth FE, Old LJ, Scott AM (2000a) In vivo bio distribution of a humanized anti-Lewis Y monoclonal antibody (hu3S193) in MCF-7 xenografted BALB/c nude mice. Cancer Res 60(17):4804–4811PubMed

Clarke K, Lee FT, Brechbiel MW, Smyth FE, Old LJ, Scott AM (2000b) Therapeutic efficacy of anti-Lewis(y) humanized 3S193 radioimmunotherapy in a breast cancer model: enhanced activity when combined with taxol chemotherapy. Clin Cancer Res 6(9):3621–3628PubMed

Co MS, Baker J, Bednarik K, Janzek E, Neruda W, Mayer P, Plot R, Stumper B, Vasquez M, Queen C, Loibner H (1996) Humanized anti-Lewis Y antibodies: in vitro properties and pharmacokinetics in rhesus monkeys. Cancer Res 56(5):1118–1125PubMed

Fiorucci S, de Lima OM, Mencarelli A Jr, Palazzetti B, Distrutti E, McKnight W, Dicay M, Ma L, Romano M, Morelli A, Wallace JL (2002) Cyclooxygenase-2-derived lipoxin A₄ increases gastric resistance to aspirin-induced damage. Gastroenterology 123(5):1598–1606CrossRefPubMed

Geng M, Wang L, Li P (2013) Correlation between chemosensitivity to anticancer drugs and Bcl-2 expression in gastric cancer. Int J Clin Exp Pathol 6(11):2554–2559PubMedCentralPubMed

Gomes J, Magalhães A, Carvalho AS, Hernandez GE, Papp SL, Head SR, Michel V, David L, Gärtner F, Touati E, Reis CA (2012) Glycophenotypic alterations induced by Pteridium aquilinum in mice gastric mucosa: synergistic effect with Helicobacter pylori infection. PLoS One 7(6):e38353CrossRefPubMedCentralPubMed

Hasegawa M, Horiki N, Tanaka K, Wakabayashi H, Tano S, Katsurahara M, Uchida A, Takei Y, Sudo A (2013) The efficacy of rebamipide add on therapy in arthritic patients with COX-2 selective inhibitor-related gastrointestinal events: a prospective, randomized, open-label blinded-endpoint pilot study by the GLORIA study group. Mod Rheumatol 23(6):1172–1178CrossRefPubMed

Hu PJ, Yu J, Zeng ZR, Leung WK, Lin HL, Tang BD, Bai AH, Sung JJ (2004) Chemoprevention of gastric cancer by celecoxib in rats. Gut 53(2):195–200CrossRefPubMedCentralPubMed

Kaneko S, Kaneko M, Fukushima T (2013) Enhanced antitumor effect of lower-dose and longer-term CPT-11 treatment in combination with low-dose celecoxib against neuroblastoma xenografts. Int J Clin Oncol 18(1):116–125CrossRefPubMed

Kelly MP, Lee FT, Smyth FE, Brechbiel MW, Scott AM (2006) Enhanced efficacy of 90Y radiolabelled anti-Lewis Y humanized monoclonal antibody hu3S193 and Palictaxel combined-modality radioimmunotherapy in a breast cancer model. J Nucl Med 47(4):716–725PubMed

Kelly MP, Lee FT, Tahtis K, Smyth FE, Brechbiel MW, Scott AM (2007) Radioimmunotherapy with alpha-particle emitting 213Bi-C-functionalized trans-cyclohexyl-diethylenetriaminepentaacetic acid-humanized 3S193 in enhanced by combination with pclitaxel chemotherapy. Clin Cancer Res 13(18 Pt 2):5604s–5612sCrossRefPubMed

Kovacic N, Muthing J, Marusic A (2000) Immunohistological and flow cytometric analysis of glycosphingolipid expression in mouse lymphoid tissues. J Histochem Cytochem 48:1677–1690CrossRefPubMed

Lee FT, Mountain AJ, Kelly MP, Hall C, Rigopoulos A, Johns TG, Smyth FE, Brechbiel MW, Nice EC, Burgess AW, Scott AM (2005) Enhanced efficacy of radioimmunotherapy with 90YA’’—DPTA-hu3S193 by inhibition of epidermal growth factor receptor (EGFR) signaling with EGFR tyrosine kinase inhibitor AG1478. Clin Cancer Res 11(19 Pt 2):7080s–7086sCrossRefPubMed

Li FF, Lin B, Hao YY, Liu JJ, Zhang F, Zhang SL (2008) Inhibitory effect of anti-Lewis y antibody on alpha1, 2-fucosyltransferase gene transfected human ovarian cancer cells in vitro. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 24(3):267–269 (in Chinese)PubMed

Lin Y, Ueda J, Kikuchi S, Totsuka Y, Wei WQ, Qiao YL, Inoue M (2011) Comparative epidemiology of gastric cancer between Japan and China. World J Gastroenterol 17(39):4421–4428CrossRefPubMedCentralPubMed

Liu J, Lin B, Hao Y, Qi Y, Zhu L, Li F, Liu D, Cong J, Zhang S, Iwamori M (2009) Lewis Y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the P13K/Akt signaling pathway. J Exp Clin Cancer Res 28:154CrossRefPubMedCentralPubMed

Loei H, Tan HT, Lim TK, Lim KH, So JB, Yeoh KG, Chung MC (2012) Mining the gastric cancer secretome: identification of GRN as potential diagnostic marker for early gastric cancer. J Proteome Res 11(3):1759–1772CrossRefPubMed

Mahmut B, Ahmet K, Fatih A, Cemal G, Ibrahim K, Durkaya O (1998) Increased serum CA 72-4 levels in patients with gastrointestinal carcinoma. J Med Sci 28:259–263

McCormack PL (2011) Celecoxib. A review of its use for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Drugs 71(18):2457–2489CrossRefPubMed

Miyoshi E, Moriwaki K, Nakagawa T (2008) Biological function of fucosylation in cancer biology. J Biochem 14:725–729

Moriwaki K, Miyoshi E (2010) Fucosylation and gastrointestinal cancer. World J Hepatol 2:151–161CrossRefPubMedCentralPubMed

Patel S, Vetale S, Teli P, Mistry R, Chiplunkar S (2012) IL-10 production in non-small cell lung carcinoma patients is regulated by ERK, P38 and COX-2. J Cell Mol Med 16(3):531–544CrossRefPubMedCentralPubMed

Peluffo GD, Stillitani I, Rodriguez VA, Diament MJ, Klein SM (2004) Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal anti-inflammatory drugs. Int J Cancer 110:825–830CrossRefPubMed

Rao CV, Indranie C, Simi B, Manning PT, Connor JR, Reddy BS (2002) Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooxygenase-2 inhibitor. Cancer Res 62(1):165–170PubMed

Rao CV, Steele VE, Swamy MV, Patlolla JM, Guruswamy S, Kopelovich L (2009) Inhibition of azoxymethane-induced colorectal cancer by CP-31398, a TP53 modulator, alone or in combination with low doses of celecoxib in male F344 rats. Cancer Res 69(20):8175–8182CrossRefPubMedCentralPubMed

Reis CA, Osorio H, Silva L, Gomes C, David L (2010) Alteration in glycosylation as biomarkers for cancer detection. J Clin Pathol 63(4):322–329CrossRefPubMed

Santos-Silva F, Fonseca A, Caffrey T, Carvalho F, Mesquita P, Reis C, Almeida R, David L, Hollingsworth MA, Thomsen F (2005) Antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism. Glycobiology 15:511–517CrossRefPubMed

Sareddy GR, Kesanakurti D, Kirti PB, Babu PP (2013) Nonsteroidal anti-inflammatory drugs diclofenac and celecoxib attenuates Wnt/b-catenin/Tcf signaling pathway in human glioblastoma cells. Neurochem Res 38(11):2313–2322CrossRefPubMed

Suerbaum S, Michetti P (2002) Helicobacter pylori infection. N Engl J Med 347(15):1175–1186CrossRefPubMed

Torres J, Leal-Herrera Y, Perez-Perez G, Gomez A, Camorlinga-Ponce M, Cedillo-Rivera R, Tapia-Conyer R, Muñoz O (1998) A community-based seroepidemiologic study of Helicobacter pylori infection in Mexico. J Infect Dis 178(4):1089–1094CrossRefPubMed

Wang J, Wang WH, Li J, Liu FX (2010) Celecoxib inhibits Helicobacter pylori colonization related factors. World J Gastroenterol 16(7):846–853PubMedCentralPubMed

Wirth HP, Yang M, Karita M, Blaser MJ (1996) Expression of the human cell surface glycoconjugates Lewis X and Lewis Y by the Helicobacter pylori isolates is related to CagA status. Infect Immun 64(11):4598–4605PubMedCentralPubMed

Wong BC, Zhang L, Ma JL, Pan KF, Li JY, Shen L, Liu WD, Feng GS, Zhang XD, Li J, Lu AP, Xia HH, Lam S, You WC (2012) Effects of selective COX-2 inhibitor and Helicobacter pylori eradication on precancerous gastric lesions. Gut 61(6):812–818CrossRefPubMed

Xiao H, Chung SY (2008) Combination regimen with statins and NSAIDs. A promising strategy for cancer chemoprevention. Int J Cancer 123(5):983–990CrossRefPubMed

Yang HB, Cheng HC, Sheu BS, Hung KH, Liou MF, Wu JJ (2007a) Chronic celecoxib users more often show regression of gastric intestinal metaplasia after Helicobacter pylori eradication. Aliment Pharmacol Ther 25(4):455–461CrossRefPubMed

Yang X, Zhang Z, Jia S, Liu Y, Wang X, Yan Q (2007b) Overexpression of fucosyltransferase IV in A431 cell line increase cell proliferation. Int J Biochem Cell Biol 39(9):1722–1730CrossRefPubMed

Yang X, Liu S, Liu YJ, Liu JW, Liu TJ, Wang XQ, Yan Q (2010) Overexpression of fucosyltransferase IV promotes A431 cell proliferation through activating MAPK and PI3K/Akt signaling pathways. J Cell Physiol 225(2):612–619CrossRefPubMed

Ye YW, Hu S, Shi YQ, Zhang XF, Zhou Y, Zhao CL, Wang GJ, Wen JG, Zong H (2013) Combination of the FGFR4 inhibitor PD173074 and 5-fluorouracil reduces proliferation and promotes apoptosis in gastric cancer. Oncol Rep 30(6):2777–2784PubMed

Zhang LJ, Wang SY, Huo XH, Zhu ZL, Chu JK, Ma JC, Cui DS, Gu P, Zhao ZR, Wang MW, Yu J (2009) Anti Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous of gastric lesions. World J Gastroenterol 15(22):2731–2738CrossRefPubMedCentralPubMed

Zhang B, Ma X, Li Z, Gao X, Wang F, Liu L, Shen G, Sang Y, Li M, Li Y, Zhao J, Wei Y (2013) Celecoxib enhances the efficacy of 15-hydroxyprostaglandin dehydrogenase gene therapy in treating murine breast cancer. J Cancer Res Clin Oncol 139(5):797–807CrossRefPubMed

Zhao Y, Hao Y, Ji H, Fang Y, Guo Y, Sha W, Zhou Y, Pang X, Southerland WM, Califano JA, Gu X (2010) Combinational effect of salvianolic acid B with low dose celecoxib on inhibition of head and neck squamous cell carcinoma growth in vitro and in vivo. Cancer Prev Res (Phila) 3(6):787–796CrossRef

Zheng X, Cui XX, Avila GE, Huang MT, Liu Y, Patel J, Kong AN, Paulino R, Shih WJ, Lin Y, Rabson AB, Reddy BS et al (2007) Atorvastatin and celecoxib inhibit prostate PC-3 tumors in immunodeficient mice. Clin Cancer Res 13:5480–5487CrossRefPubMed

Titel: Anti-LeY antibody enhances therapeutic efficacy of celecoxib against gastric cancer by downregulation of MAPKs/COX-2 signaling pathway: correlation with clinical study
verfasst von: Faisal Aziz
Xuesong Yang
Xiaoqi Wang
Qiu Yan
Publikationsdatum: 01.07.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-014-1892-z

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Anti-LeY antibody enhances therapeutic efficacy of celecoxib against gastric cancer by downregulation of MAPKs/COX-2 signaling pathway: correlation with clinical study

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Material and Methods

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Conclusions

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