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【转贴】锌可预防食道和口腔癌
Dietary Zinc Modulation of COX-2 Expression and Lingual and Esophageal Carcinogenesis in Rats
最近，杰斐逊医学院和Kimmel癌症中心的研究人员发现锌可以有助预防高危个体的食道和口腔癌症。口腔和食道癌与营养性锌缺乏有关，而且COX-2酶表达的上升也与这些癌症相联系。Louise Fong等人发现让缺乏锌的大鼠口服锌能够抑制食道和口腔前癌症状的发展并且还同时降低了COX-2的表达水平。
这些发现表明锌的补充可能预防食道或口腔癌的发展，这些癌症在锌缺乏的发展中国家是一个突出的问题。研究人员将发现公布在2005年1月5日的Journal of the National Cancer Institute上。
人类摄入的锌通常来自红肉和海产品。然而，大约10％的美国人的饮食缺乏锌，而在发展中国家则有约20亿人缺乏锌。流行病学研究表明最近若干年，食道和口腔癌发病率处于不断上升的趋势。而且，每年大约有13000名美国人死于食道和口腔癌。
Fong博士一直致力于研究锌缺乏和它与食道癌的联系，并且构建出了锌缺乏和癌症敏感性动物模型。锌的缺乏会增加食道和口腔的细胞扩增，从而使这些区域对致癌物质敏感，因此增加了癌症发展的风险。
Fong博士对正常大鼠和锌缺乏大鼠的食道和舌头组织中的COX-2蛋白和基因表达情况进行了比较。他们发现锌缺乏大鼠的COX-2表达水平增加了10到15倍。细胞扩增水平也同时增加。在让缺锌大鼠服用锌后，COX-2的表达显著降低并且前癌细胞增殖也发生了逆转。研究人员还发现用COX-2抑制剂处理的大鼠，其COX-2和细胞增殖水平都下降了。
试验证明锌治疗恢复了受锌缺乏影响的许多系统。接下来，研究人员还将调查锌与低量的celcoxib（COX-2抑制剂）联合使用对消化道癌症的预防效果。
ARTICLE
Dietary Zinc Modulation of COX-2 Expression and Lingual and Esophageal Carcinogenesis in Rats
Louise Y. Y. Fong, Liang Zhang, Yubao Jiang, John L. Farber
Affiliation of authors: Kimmel Cancer Center and Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA
Correspondence to: Louise Y. Y. Fong, Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust St., Philadelphia, PA 19107 (e-mail: louise.fong@jefferson.edu)
Background: Cancer of the upper aerodigestive tract, including esophageal and tongue carcinomas, is a major cause of cancer deaths worldwide. Esophageal and tongue cancers have both been associated with dietary zinc deficiency (ZD), and cyclooxygenase (COX-2) is often overexpressed in these cancers. Using rat models, we examined whether zinc regulates COX-2 expression in these cancers. Method: Expression of COX-2 protein and mRNA in rat lingual and esophageal epithelia in control (zinc sufficient [ZS]) rats, during ZD, and after intragastric zinc replenishment (ZR) were determined by immunoblotting, immunohistochemistry, and real-time quantitative polymerase chain reaction. COX-2 gene expression, cell proliferation, and apoptosis were analyzed in ZD, ZR, and ZD rats treated with the COX-2 inhibitors celecoxib and indomethacin. Tumor development in ZD rats treated by continuous exposure to the carcinogen 4-nitroquinoline 1 oxide (NQO), which causes tongue tumors in rats, was compared with those in NQO-treated ZS rats. Statistical tests were two-sided. Results: The esophagus and tongue of ZD rats were hyperplastic and expressed COX-2 protein and mRNA at 8- to 14.7-fold higher levels than control rats. Within hours ZR reduced COX-2 overexpression to threefold that in control rats and reversed the hyperplastic phenotypes. The esophagus of ZD rats treated with celecoxib or indomethacin showed a reduction in cell proliferation and stimulation of apoptosis. NQO treatment resulted in greater incidence of lingual squamous cell carcinomas (74% versus 22%, difference = 52%, 95% confidence interval [CI] = 20% to 80%, P = .015) and greater tumor multiplicity (13.1 versus 4.3, difference = 8.8, 95% CI = 7.0 to 10.6, P = .018) in ZD than ZS rats. Of 23 NQO-treated ZD rats, 39% (9) and 61% (14) harbored esophageal and forestomach tumors, respectively, whereas none of the NQO-treated ZS rats did. Conclusions: COX-2 overexpression accompanies hyperplasia in ZD rats. Increased cell proliferation in NQO-treated ZD rats facilitates the development of tumors at multiple sites. The finding that zinc regulates COX-2 expression in vivo in an animal model may lead to prevention or therapeutic possibilities for upper aerodigestive tract cancer.
http://jncicancerspectrum.oupjournals.org/cgi/content/abstract/jnci;97/1/40
http://jncicancerspectrum.oupjournals.org/cgi/content/full/jnci;94/4/248
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作者:admin@医学,生命科学 2011-06-17 18:08
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