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首页> 外文学位 >An investigation of the effects of vitamin E succinate (VES) on human prostate LNCaP tumor growth and gene expression in BALB/c nude mice fed high-fat diets.
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An investigation of the effects of vitamin E succinate (VES) on human prostate LNCaP tumor growth and gene expression in BALB/c nude mice fed high-fat diets.

机译：研究维生素E琥珀酸酯（VES）对高脂饮食喂养的BALB / c裸鼠中人前列腺LNCaP肿瘤生长和基因表达的影响。

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摘要

Prostate cancer is the most diagnosed form of noncutaneous malignancy and the second leading cause of cancer death among men in the United States. The primary treatment modalities are not effective for some forms of the disease. Identification of alternate approaches such as the chemoprotective agent alpha-tocopheryl succinate (alpha-TOS) has become attractive. We studied the effects of alpha-TOS treatment on the growth and gene expression of human prostate LNCaP tumor cells in BALB/c nu/nu male mice (9 weeks old, n = 48) fed 20% fat (SBO or CSO) diets. Mice received subcutaneous inoculations of LNCaP tumor cells in Matrigel matrix and were randomly divided into four groups (20%-SBO, 20%-SBO+alpha-TOS, 20%-CSO, and 20%-CSO+alpha-TOS, n=12/group). On day 21 after the inoculation of LNCaP cells, groups 20%-SBO+alpha-TOS and 20%-CSO+alpha-TOS received intraperitoneal (ip) injection of alpha-TOS (100 mg/kg body weight) in sesame oil three times a week and groups 20%-SBO and 20%-CSO received sesame oil vehicle three times a week. At day 56 mice were sacrificed, livers and tumors were harvested, weighed and snap frozen in liquid nitrogen or stored in RNA later for hepatic tocopherol analysis by high performance liquid chromatography (HPLC) and real-time polymerase chain reaction (RT-qPCR), respectively. Quantitative comparisons of mRNA relative expressions of target genes were performed using the comparative 2-DeltaDeltaC(t) method. Combination of the 20%-CSO diet with alpha-TOS treatment resulted in modest reduction of mRNA expressions of both PSA and AR, and a more pronounced reductions of mRNA expressions in VEGF-total, VEGF-165, IGF-1B and TGF-beta1 genes. The use of 20%-CSO diet with vehicle-control also led to reduction in mRNA expressions of the target genes. Results from HPLC analysis of liver samples show that ip administration of alpha-TOS in our mouse model greatly increased the alpha-TOH hepatic pool and led to alpha-TOS storage in the liver. Taken together, these results indicate that both 20%-CSO diet and alpha-TOS treatment individually and in combination down regulated the studied genes and impacted the bioavailability of alpha-TOH in the body suggesting the relevance of these bioactive compounds as adjuvant chemotherapeutic agents in the treatment of prostate cancer.
机译：在美国，前列腺癌是最被诊断的非皮肤恶性肿瘤形式，也是癌症死亡的第二大主要原因。主要治疗方式对某些形式的疾病无效。鉴定诸如化学保护剂琥珀酸α-生育酚酸酯（α-TOS）之类的替代方法变得有吸引力。我们研究了α-TOS处理对饲喂20％脂肪（SBO或CSO）饮食的BALB / c nu / nu雄性小鼠（9周大，n = 48）中人前列腺LNCaP肿瘤细胞的生长和基因表达的影响。小鼠接受Matrigel基质中LNCaP肿瘤细胞的皮下接种，随机分为四组（20％-SBO，20％-SBO + alpha-TOS，20％-CSO和20％-CSO + alpha-TOS，n = 12 /组）。在接种LNCaP细胞后的第21天，将20％-SBO + alpha-TOS和20％-CSO + alpha-TOS组接受腹腔内（ip）注射芝麻油中的alpha-TOS（100 mg / kg体重）。每周两次，小组20％-SBO和20％-CSO每周接受3次芝麻油媒介。在第56天，处死小鼠，收获肝脏和肿瘤，称重并在液氮中速冻，或稍后存储在RNA中，以通过高效液相色谱（HPLC）和实时聚合酶链反应（RT-qPCR）进行肝生育酚分析，分别。使用比较2-DeltaDeltaC（t）方法进行靶基因的mRNA相对表达的定量比较。 20％-CSO饮食与alpha-TOS治疗相结合会导致PSA和AR的mRNA表达适度降低，而VEGF-total，VEGF-165，IGF-1B和TGF-beta1中的mRNA表达则更为明显地降低基因。具有媒介物控制的20％-CSO饮食的使用还导致靶基因的mRNA表达下降。肝脏样品的HPLC分析结果表明，在我们的小鼠模型中腹膜内施用alpha-TOS大大增加了alpha-TOH肝库，并导致alpha-TOS在肝脏中的储存。综上所述，这些结果表明，单独或联合使用20％-CSO饮食和α-TOS治疗均会下调所研究的基因并影响体内α-TOH的生物利用度，表明这些生物活性化合物作为佐剂的化学治疗意义重大。前列腺癌的治疗。

著录项

  • 作者

    Aredo, Bogale.;

  • 作者单位

    Texas Woman's University.;

  • 授予单位 Texas Woman's University.;
  • 学科 Biology Molecular.;Health Sciences Nutrition.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 141 p.
  • 总页数 141
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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