番茄红素与肿瘤的关系

2010-02-12

最早有关番茄红素抗肿瘤的生物活性的报导是在1959年，Ernster和Lind-berg等发现辐射后的小鼠腹腔内注射番茄红素后生存率提高了，并能抵抗细菌的感染。他们的工作整理成两篇论文，发表如下：

u Modification of the x-irradiation syndrome by lycopene. Exp Cell Res 1959 Jan; 16(1): 7-14.4.

u The promoting effect of lycopene on the non-specific resistance of animals. Exp Cell Res 1959 Feb; 16(2):384-93.4.

到了上世纪80年代初，研究者们开始认为番茄红素的抗氧化作用可以帮助降低DNA突变的概率，从而达到降低肿瘤发病风险，同时也能降低因脂蛋白氧化而引起的心血管疾病。于是开始了许多流行性病学的研究，查看绿色和黄色蔬菜水果的摄入量与肿瘤发病率之间的关系。

1985年，一项有关美国老年人的流行病学研究显示，高剂量摄食番茄与癌症死亡率的显著下降有关。

u Colditz GA, et al. Increased green and yellow vegetables intake and lowered cancer death in an elderly population. Am J Clin Nutr 1985；41: 32-36.
http://www.ajcn.org/cgi/reprint/41/1/32.pdf

许多流行病学和临床研究的证据都指向摄食番茄制品可以降低肿瘤发病的风险，尤其是胃肠道和前列腺癌，而番茄红素是番茄制品中的主要类胡萝卜素。于是大量研究成果的积累，慢慢让大家理解番茄红素与肿瘤之间的关系，并受到越来越多的重视。

u 1989年，Morris等开始收集肿瘤病人血清中各种营养因子的浓度生化资料，番茄红素也被列入其中，发现肿瘤患者血清中有偏低的趋势。
Kathy J, et al. Selenium, lycopene, a-tocopherol, β-carotene, retinol, and subsequent bladder cancer. Cancer Res 1989; 49: 6144-6148.
http://cancerres.aacrjournals.org/cgi/reprint/49/21/6144

u 1991年，Campbell等发现乳腺癌患者的血清中类胡萝卜素的含量较正常人低。
Potischman N, et al. Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A. Am J Clin Nutr 52:909–915, 1990.
http://www.ajcn.org/cgi/reprint/52/5/909

u 1992年，VanEenwyk等的研究也发现，血清中番茄红素含量与子宫颈癌、膀胱癌的风险率呈负相关。
VanEenwyk J, et al. Folate, Vitamin C, and cervical intraepithelial neoplasia. Cancer Epidem Biomar 1992；1：119-124.

http://cebp.aacrjournals.org/cgi/reprint/1/2/119

u 1994年，从1985年起研究了多年的意大利科研人员报导了消化道癌发生率的降低与番茄酱的高摄入量有关。
Franceschi S, et al. Tomatoes and risk of digestive-tract cancers. Int J Cancer 1994; 59: l8l- l84.
http://www3.interscience.wiley.com/journal/112706964/abstract

重要的研究进展出现在1995年。

Giovannucci等在美国健康职业跟踪研究中确证番茄制品的高摄取量与肿瘤风险率呈负相关，进一步研究表明，总胡萝卜素、β-胡萝卜素、α-胡萝卜素、叶黄素以及β-隐黄质的摄食量与风险因子没有关系，降低肿瘤的关键因子是番茄红素。

u Giovannucci E, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J. Natl. Cancer Inst. 1995; 87: 1767-1776.
http://jnci.oxfordjournals.org/cgi/content/abstract/87/23/1767

u Zhang SM, et al. Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. Am J Clin Nutr 1997; 66: 626-632.
http://www.ajcn.org/cgi/reprint/66/3/626

到了1999年，流行病学的研究就有了很好的总结，确认番茄红素才是预防肿瘤的主角。

u Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: Review of the epidemiologic literature. J Natl Cancer Inst 1999; 91: 317–31.
http://jnci.oxfordjournals.org/cgi/reprint/91/4/317

u Michaud DS, et al. Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am J Clin Nutr 2000; 72: 990–997.
http://www.ajcn.org/cgi/reprint/72/4/990

于是，调查番茄红素对肿瘤细胞的直接杀伤，成为了近10年的研究热门，已经有数不清的相关论文发表，下面列举数篇:

u Kotake -Nara K, et al. Carotenoids affect proliferation of human prostate cancer cells. J Nutr. 2001; 131:3303-3306.
http://jn.nutrition.org/cgi/content/abstract/131/12/3303

u Tan LL, et al. Lycopene inhibits the growth of human androgen-independent prostate cancer cells in vitro and in BALB/c nude mice. J. Nutr. 2005; 135:287-290.

http://jn.nutrition.org/cgi/reprint/135/2/287

u Chalabi N, et al. The effects of lycopene on the proliferation of human breast cells and BRCA1 and BRCA2 gene expression. Eur J Cancer 2006; 40: 1768-1775.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T68-4CP0YVH-4&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=940427411&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=31e42dae9646b23daaf340a4d3e83a7d

u Hwang ES, et al. Inhibitory effects of lycopene on the adhesion, invasion, and migration of SK-Hep1 human hepatoma cells. Exp Biol Med 2006; 231: 322-327.
http://www.ebmonline.org/cgi/reprint/231/3/322

u Salman H, et al. Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed & Pharmacother 2007; 61: 366-369.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VKN-4N972MM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=940387411&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=c4722f13cdc420ee1b2944aa4aab712e

u Forneli F, et al. The influence of lycopene on the proliferation of human breast cell line (MCF-7). Toxicol in vitro 2007; 21: 217-223.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCP-4M27HBC-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=940418954&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=68d50d963431ed37078ef5bd9e073b93

u Palozza P, et al. The growth-inhibitory effects of tomatoes digested in vitro in colon adenocarcinoma cells occur through down regulation of cyclin D1, Bcl-2 and Bcl-xL. British J Nut 2007; 98: 789–795.
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=1343148

但是这些体内或体外的实验中番茄红素起作用的浓度均比较高，也因此可以推测，其实可能还有其他因子共同作用。

直到2008年，终于有了第一篇这样的报导，说明番茄红素单独抗肿瘤的效果有限，必须与其他物质配合在一起才有更好的抗肿瘤表现。

u Mossine VV, et al. Interaction of tomato lycopene and ketosamine against rat prostate tumorigenesis. Cancer Res 2008; 68: 4384-4391.
http://cancerres.aacrjournals.org/cgi/reprint/68/11/4384

u Venkateswaran V, et al. A Combination of micronutrients is beneficial in reducing the incidence of prostate cancer and increasing survival in the lady transgenic model. Cancer Prev Res 2009; 2: 473-483.

http://www.ncbi.nlm.nih.gov/pubmed/19401531

最近又有研究证明，番茄红素可以调控肿瘤细胞增殖相关的基因表达来达到抑制肿瘤生长的效果。

u Audrey KB, et al. Modulation of gene methylation by genistein or lycopene in breast cancer cells. Environ Mol Mutagen 2008; 49:36-45.
http://www3.interscience.wiley.com/journal/117881784/abstract?CRETRY=1&SRETRY=0