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学科主题: 临床医学
题名:
Effect of lycopene on androgen receptor and prostate-specific antigen velocity
作者: Zhang Xin1,2; Wang Qi3; Neil, Barber4; Chen Xiao1,2
关键词: lycopene ; prostate cancer ; LnCaP ; androgen receptor element
刊名: CHINESE MEDICAL JOURNAL
发表日期: 2010-08-20
DOI: 10.3760/cma.j.issn.0366-6999.2010.16.014
卷: 123, 期:16, 页:2231-2236
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, General & Internal
研究领域[WOS]: General & Internal Medicine
关键词[WOS]: CANCER CELL-LINE ; IN-VITRO ; CARCINOMA-CELLS ; CAROTENOIDS ; GROWTH ; RISK ; PROLIFERATION ; RETINOL
英文摘要:

Background There is increasing interest in the role of dietary factors in both the development and behaviour of prostate cancer This study was carried out to evaluate the impact of the dietary factor lycopene on DNA synthesis, activity and expression of the androgen receptor gene element in prostate LnCaP cells and to report our pilot phase II study investigating its effect on prostate-specific antigen velocity over one year

Methods LnCaP cells were grown with or without different concentrations of lycopene or tetrahydrofuran (THF solvent) added to the culture medium for 48 hours. DNA synthesis was measured by the incorporation of bromodeoxyuridine (Brdu) into DNA during a 4-hour pulse, followed by immunostaining and visualization of stained cells using fluorescence microscopy A transient transfection of a plasmid DNA recombinant containing an androgen receptor element-luciferase (ARE-Luc) report gene into LnCaP cells was developed and the impact of different concentrations of lycopene on the androgen receptor element was reflected by quantitative analysis of the luciferase enzyme function Expression of the androgen gene was also studied by Western blotting. The phase II pilot study patients (n=41) previously diagnosed with prostate cancer were enrolled and given lycopene supplement, 10 mg per day, and response was measured by observing changes in the plasma prostate-specific antigen (PSA) levels

Results The addition of 0.5 mu mol/L, 5 mu mol/L, 10 mu mol/L and 15 mu mol/L of lycopene was shown to inhibit cell growth by 2.66%, 4 29%, 3 73% and 13.66%, respectively, compared with the THF solvent control samples (P=0 015). As compared with the RPMI1640 medium group, cell proliferation in the presence of 5 mu mol/L, 10 mu mol/L, and 15 mu mol/L lycopene was inhibited by 8.12%, 6.33% and 12.00%, respectively (P=0.024). We showed for the first time that lycopene inhibited the activity of the androgen receptor gene element in a dose-related manner. Inhibition was seen in the transcription of the luciferase construct and confirmed by androgen receptor element expression assayed by Western blotting Regression slopes of (log) PSA vs. time decreased in 26/37 (70%, 95% Cl 53%-84%) of the patients after supplementation and in eight cases (21%) the post-treatment slope was negative For these eight patients, the average fall in PSA was equivalent to 2% over 28 days (i.e. an average slope/d of -0 000 713) The Wilcoxon rank-sum test showed an overall statistically significant decrease in slope (P=0 0007). Analysis of the PSA doubling time (pretreatment vs posttreatment) showed a median increase after supplementation for 174 days, however, this was not statistically significant (P=0 18).

Conclusions Lycopene as an antioxidant dietary factor could significantly inhibit DNA synthesis in a dose-dependent pattern, the result revealed lycopene might inhibit androgen receptor gene element activity and expression Dietary lycopene may play an important role in prostate cancer cell proliferation and further supports a large randomized study into the role of lycopene supplementation in malignant prostate disease

语种: 英语
所属项目编号: 2004-B-01
项目资助者: Beijing Science and Technology Committee
WOS记录号: WOS:000281488300014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51322
Appears in Collections:北京大学临床肿瘤学院_泌尿外科_期刊论文

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作者单位: 1.Beijing Canc Hosp, Dept Urol, Beijing 100142, Peoples R China
2.Kings Coll Hosp London, Dept Urol, London, England
3.Peking Univ, Sch Oncol, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 100142, Peoples R China
4.Capital Med Univ, Dept Urol, Beijing Xuanwu Hosp, Beijing 100053, Peoples R China

Recommended Citation:
Zhang Xin,Wang Qi,Neil, Barber,et al. Effect of lycopene on androgen receptor and prostate-specific antigen velocity[J]. CHINESE MEDICAL JOURNAL,2010,123(16):2231-2236.
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