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Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases.
Oral Oncol. 2008 Jul; 44(7):652-7.OO

Abstract

Oral cancer is a common neoplasm worldwide with tobacco and alcohol being the major etiological factors contributing to its pathogenesis. Epidermal growth factor receptor (EGFR) and ErbB2 are known to be involved in the development of oral cancer with the former up-regulated in up to 90% human cases. The goal of this study was to evaluate the chemopreventive effects of a dual inhibitor of EGFR and ErbB2 tyrosine kinases, GW2974, in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch model. A short-term experiment (3-week topical DMBA followed by 1-week topical GW2974) was conducted to examine the effects of GW2974 on aberrant arachidonic acid (AA) metabolism and cell proliferation in the hamster oral epithelium. Topical application of 0.1 ml GW2974 (160 microM, three times a week) significantly reduced the levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 5-, 12-, 15-hydroxyeicosatetraenoic acid (HETE), and cell proliferation (BrdU-labeling index). In a long-term post-initiation experiment (6-week topical DMBA followed by 18-week topical GW2974), GW2974 (4 mM and 8 mM) significantly inhibited the incidence, number and size of visible tumors. Under microscope, the numbers of oral lesions (hyperplasia, dysplasia, carcinoma) and the incidence of squamous cell carcinoma (SCC) were also significantly suppressed by GW2974. In summary, our study indicated that dual inhibition of EGFR and ErbB2 tyrosine kinases by GW2974 was effective in preventing oral carcinogenesis in DMBA-induced hamster cheek pouch model. GW2974 exerted its chemopreventive effects in part by suppressing aberrant AA metabolism.

Authors+Show Affiliations

Cancer Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC 27707, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17936675

Citation

Sun, Zheng, et al. "Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced Oral Carcinogenesis in Hamster Cheek Pouch By Topical Application of a Dual Inhibitor of Epidermal Growth Factor Receptor (EGFR) and ErbB2 Tyrosine Kinases." Oral Oncology, vol. 44, no. 7, 2008, pp. 652-7.
Sun Z, Sood S, Li N, et al. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases. Oral Oncol. 2008;44(7):652-7.
Sun, Z., Sood, S., Li, N., Yang, P., Newman, R. A., Yang, C. S., & Chen, X. (2008). Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases. Oral Oncology, 44(7), 652-7.
Sun Z, et al. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced Oral Carcinogenesis in Hamster Cheek Pouch By Topical Application of a Dual Inhibitor of Epidermal Growth Factor Receptor (EGFR) and ErbB2 Tyrosine Kinases. Oral Oncol. 2008;44(7):652-7. PubMed PMID: 17936675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases. AU - Sun,Zheng, AU - Sood,Sandeep, AU - Li,Ning, AU - Yang,Peiying, AU - Newman,Robert A, AU - Yang,Chung S, AU - Chen,Xiaoxin, Y1 - 2007/10/23/ PY - 2007/06/05/received PY - 2007/08/21/revised PY - 2007/08/22/accepted PY - 2007/10/16/pubmed PY - 2009/1/30/medline PY - 2007/10/16/entrez SP - 652 EP - 7 JF - Oral oncology JO - Oral Oncol. VL - 44 IS - 7 N2 - Oral cancer is a common neoplasm worldwide with tobacco and alcohol being the major etiological factors contributing to its pathogenesis. Epidermal growth factor receptor (EGFR) and ErbB2 are known to be involved in the development of oral cancer with the former up-regulated in up to 90% human cases. The goal of this study was to evaluate the chemopreventive effects of a dual inhibitor of EGFR and ErbB2 tyrosine kinases, GW2974, in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch model. A short-term experiment (3-week topical DMBA followed by 1-week topical GW2974) was conducted to examine the effects of GW2974 on aberrant arachidonic acid (AA) metabolism and cell proliferation in the hamster oral epithelium. Topical application of 0.1 ml GW2974 (160 microM, three times a week) significantly reduced the levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 5-, 12-, 15-hydroxyeicosatetraenoic acid (HETE), and cell proliferation (BrdU-labeling index). In a long-term post-initiation experiment (6-week topical DMBA followed by 18-week topical GW2974), GW2974 (4 mM and 8 mM) significantly inhibited the incidence, number and size of visible tumors. Under microscope, the numbers of oral lesions (hyperplasia, dysplasia, carcinoma) and the incidence of squamous cell carcinoma (SCC) were also significantly suppressed by GW2974. In summary, our study indicated that dual inhibition of EGFR and ErbB2 tyrosine kinases by GW2974 was effective in preventing oral carcinogenesis in DMBA-induced hamster cheek pouch model. GW2974 exerted its chemopreventive effects in part by suppressing aberrant AA metabolism. SN - 1368-8375 UR - https://www.unboundmedicine.com/medline/citation/17936675/Chemoprevention_of_712_dimethylbenz[a]anthracene__DMBA__induced_oral_carcinogenesis_in_hamster_cheek_pouch_by_topical_application_of_a_dual_inhibitor_of_epidermal_growth_factor_receptor__EGFR__and_ErbB2_tyrosine_kinases_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1368-8375(07)00232-1 DB - PRIME DP - Unbound Medicine ER -