The Potent Anti-Tumor Effects of Rhodiola Drinking Are Associated with the Inhibition of the mTOR Pathway and Modification of Tumor Metabolism in the UPII-Mutant Ha-Ras Model.
The Potent Anti-Tumor Effects of Rhodiola Drinking Are Associated with the Inhibition of the mTOR Pathway and Modification of Tumor Metabolism in the UPII-Mutant Ha-Ras Model.
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膀胱癌主要发生在老年人中，治疗费用昂贵。瑞典草药红景天 (SHR-5) 是一种来自瑞典草药研究所（瑞典哥德堡 SHI）的标准化红景天提取物，一直处于治疗轻度至中度抑郁症和身心疲劳的临床研究中。先前的研究表明，SHR-5 通过一种与饮食限制无关的机制延长了果蝇的寿命。在这项研究中，我们检查了饮用 SHR-5 是否可以延缓浅表性膀胱癌小鼠模型中的肿瘤发展。每天饮用SHR-5可显着提高膀胱肿瘤小鼠的存活率，绝对提高61.7%，并减少尿路梗阻和肿瘤负荷。 SHR-5 饮用后通过抑制 mTOR 重塑肿瘤代谢，导致肿瘤细胞增殖减少。背景：SHR-5 已被用作增强健康人群身心表现以及对抗压力的“适应原”。本研究的目的是确定 SHR-5 对浅表性膀胱癌的化学预防功效并研究潜在的作用机制。方法：UPII 突变型 Ha-ras 膀胱癌转基因小鼠产生低度、非侵袭性乳头状移行尿路上皮细胞癌，用含 1.25 和 6.25 mg/mL SHR-5 的饮用水喂养 6 个月。通过病理学、分子、代谢和统计分析评估小鼠的存活率、梗阻性尿路病、肿瘤负荷和形态以及增殖。结果：每天饮用 SHR-5 的雄性 UPII 突变 Ha-ras 小鼠中，约 95% 或更多的小鼠存活超过 6 个月，而饮用正常水的小鼠中，只有 33.3% 存活超过 6 个月（p < 0.0001）； SHR-5 饮酒暴露还可以减轻荷瘤膀胱重量和尿路梗阻，并抑制肿瘤组织中的 mTOR 信号传导。整体代谢分析显示，SHR-5 导致酚类代谢物增加和 CoA 减少，CoA 是脂质代谢的关键代谢辅因子。结论：我们的研究结果强调了 SHR-5 作为抗衰老剂通过抑制 mTOR 信号传导重塑肿瘤代谢来预防膀胱癌的潜力。全局代谢组学分析为研究复杂草药提取物的作用机制提供了独特而有效的工具。
Bladder cancer occurs mainly in older people and is expensive to manage. Swedish Herbal Rhodiola-5 (SHR-5), a standardized Rhodiola Rosea extract from the Swedish Herbal Institute (the SHI, Gothenburg, Sweden), has been in clinical studies for managing mild to moderate depression and physical and mental fatigue. Previous studies have shown that SHR-5 extended the life span of the fruit fly through a mechanism that was not associated with dietary restriction. In this study, we examined whether drinking SHR-5 can delay tumor development in a superficial bladder cancer mouse model. Drinking SHR-5 daily markedly improved the survival rate of the bladder tumor-bearing mice, by an absolute 61.7%, and reduced urinary tract obstruction and tumor burden. SHR-5 drinking reshaped the tumor metabolism via the inhibition of the mTOR leading to a decreased tumor cell proliferation. Background: SHR-5 has been used as an “adaptogen” for enhancing physical and mental performance and for fighting stress in the healthy population. The purpose of this study is to determine the chemopreventive efficacy of SHR-5 for superficial bladder cancer and to investigate the underlying mechanisms of action. Methods: UPII-mutant Ha-ras bladder-cancer-transgenic mice, that developed low-grade and noninvasive papillary transitional urothelial cell carcinoma, were fed with 1.25 and 6.25 mg/mL SHR-5 in drinking water for 6 months. The survival of the mice, obstructive uropathy, tumor burden and morphology, and proliferation were evaluated by pathological, molecular, metabolic, and statistical analyses. Results: Approximately 95% or more of the male UPII-mutant Ha-ras mice that drank SHR-5 daily survived over 6 months of age, while only 33.3% of those mice that drank normal water survived over 6 months of age (p < 0.0001); SHR-5 drinking exposure also reduced tumor-bearing bladder weight and urinary tract obstruction and inhibited mTOR signaling in neoplastic tissues. Global metabolic analysis revealed that SHR-5 resulted in increased phenolic metabolites and decreased CoA, a critical metabolic cofactor for lipid metabolism. Conclusions: Our findings highlight the potential of SHR-5 as an anti-aging agent for bladder cancer prevention through reshaping tumor metabolism via the inhibition of the mTOR signaling. Global metabolomics profiling provides a unique and efficient tool for studying the mechanisms of complex herb extracts’ action.
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影响因子：
--
作者：
Li Y;Pham V;Bui M;Song L;Wu C;Walia A;Uchio E;Smith-Liu F;Zi X
通讯作者：
Zi X
影响因子：
4.6
作者：
Jafari M;Juanson Arabit JG;Courville R;Kiani D;Chaston JM;Nguyen CD;Jena N;Liu ZY;Tata P;Van Etten RA
通讯作者：
Van Etten RA
DOI：
10.1186/2046-2395-2-5
发表时间：
2013-04-02
期刊：
Longevity & healthspan
影响因子：
--
作者：
Gospodaryov DV;Yurkevych IS;Jafari M;Lushchak VI;Lushchak OV
通讯作者：
Lushchak OV
影响因子：
4.6
作者：
Liu, Zhongbo;Song, Liankun;Xie, Jun;Wu, Xue-Ru;Gin, Greg E.;Wang, Beverly;Uchio, Edward;Zi, Xiaolin
通讯作者：
Zi, Xiaolin
影响因子：
5.2
作者：
Huan J;Grivas P;Birch J;Hansel DE
通讯作者：
Hansel DE