饮食中的番茄红素或番茄并不能减缓小鼠模型中去势抵抗性前列腺癌的进展。
Dietary Tomato or Lycopene Do Not Reduce Castration-Resistant Prostate Cancer Progression in a Murine Model.
机构信息
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
出版信息
J Nutr. 2020 Jul 1;150(7):1808-1817. doi: 10.1093/jn/nxaa107.
BACKGROUND
Dietary tomato products or lycopene protect against prostate carcinogenesis, but their impact on the emergence of castration-resistant prostate cancer (CRPC) is unknown.
OBJECTIVE
We hypothesized that tomato or lycopene products would reduce the emergence of CRPC.
METHODS
Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were castrated at 12-13 wk and the emergence of CRPC was monitored by ultrasound in each study. In Study 1, TRAMP mice (n = 80) were weaned onto an AIN-93G-based control diet (Con-L, n = 28), a 10% tomato powder diet (TP-L, 10% lyophilized w/w, n = 26), or a control diet followed by a tomato powder diet after castration (TP-Int1, n = 26). In Study 2, TRAMP mice (n = 85) were randomized onto a control diet with placebo beadlets (Con-Int, n = 29), a tomato diet with placebo beadlets (TP-Int2, n = 29), or a control diet with lycopene beadlets (Lyc-Int, n = 27) following castration (aged 12 wk). Tumor incidence and growth were monitored by ultrasound beginning at an age of 10 wk. Mice were euthanized 4 wk after tumor detection or aged 30 wk if no tumor was detected. Tissue weights were compared by ANOVA followed by Dunnett's test. Tumor volumes were compared using generalized linear mixed model regression.
RESULTS
Ultrasound estimates for the in vivo tumor volume were strongly correlated with tumor weight at necropsy (R2 = 0.75 and 0.94, P <0.001 for both Studies 1 and 2, respectively). Dietary treatments after castration did not significantly impact cancer incidence, time to tumor detection, or final tumor weight.
CONCLUSIONS
In contrast to studies of de novo carcinogenesis in multiple preclinical models, tomato components had no significant impact on the emergence of CRPC in the TRAMP model. It is possible that specific mutant subclones of prostate cancer may continue to show some antiproliferative response to tomato components, but further studies are needed to confirm this.
背景
膳食番茄制品或番茄红素可预防前列腺癌发生，但它们对去势抵抗性前列腺癌（CRPC）的发生的影响尚不清楚。
目的
我们假设番茄或番茄红素制品可减少 CRPC 的发生。
方法
12-13 周龄转基因腺癌前列腺小鼠（TRAMP）去势，通过超声监测各研究中 CRPC 的发生情况。在研究 1 中，TRAMP 小鼠（n=80）断奶后给予AIN-93G 基础对照饮食（Con-L，n=28）、10%番茄粉饮食（TP-L，10%冻干 w/w，n=26）或去势后给予对照饮食加番茄粉饮食（TP-Int1，n=26）。在研究 2 中，TRAMP 小鼠（n=85）随机分为对照饮食加安慰剂微丸（Con-Int，n=29）、番茄饮食加安慰剂微丸（TP-Int2，n=29）或去势后给予对照饮食加番茄红素微丸（Lyc-Int，n=27）。从 10 周龄开始，通过超声监测肿瘤发生率和生长情况。如果未检测到肿瘤，则在肿瘤检测后 4 周或 30 周龄时处死小鼠。采用方差分析后 Dunnett 检验比较组织重量，采用广义线性混合模型回归比较肿瘤体积。
结果
体内肿瘤体积的超声估计值与尸检时的肿瘤重量具有强相关性（研究 1 和研究 2 的 R2分别为 0.75 和 0.94，P<0.001）。去势后给予饮食处理并未显著影响癌症发生率、肿瘤检测时间或最终肿瘤重量。
结论
与多个临床前模型中新发癌症的研究结果相反，番茄成分对 TRAMP 模型中 CRPC 的发生没有显著影响。可能是前列腺癌的特定突变亚克隆仍对番茄成分表现出一定的抗增殖反应，但需要进一步研究证实这一点。
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