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The role of folate and folylpoly-gamma-glutamate synthetase (FPGS) in the chemotherapeutics of human colon cancer cells.

机译：叶酸和叶酰聚γ-谷氨酸合成酶（FPGS）在人类结肠癌细胞的化学治疗中的作用。

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Folylpoly-gamma-glutamate synthetase (FPGS) is essential in (anti)-folate polyglutamation and intracellular retention. Folylpolyglutamates are preferred substrates for DNA methylation and synthesis, and anti folylpolyglutamates confer cytotoxicity. The present research investigated the role of folate and FPGS in the chemotherapeutics of human colon cancer cells. The effect of folate deficiency on endogenous FPGS levels, and altered FPGS levels on chemosensitivity were examined. Folate deficiency reduced FPGS expression in Caco2 and HCT116 human colon cancer cells and FPGS activity only in Caco2 cells. An in vitro model of altered FPGS levels in HCT116 cells was developed and its biochemical properties described. Sense human FPGS cDNA conferred up-regulation of FPGS expression and activity, increased intracellular folate concentration, enhanced polyglutamation, increased growth rate and enhanced chemosensitivity to 5-fluorouracil compared with antisense hFPGS cells. Collectively, these data contribute to the current understanding of the role of folate and FPGS in the chemotherapeutics of human colon cancer cells.

机译：聚谷氨酸-γ-谷氨酸合成酶（FPGS）在（抗）-叶酸聚谷氨酸和细胞内滞留中至关重要。聚叶谷氨酸是DNA甲基化和合成的优选底物，并且抗叶基聚谷氨酸赋予细胞毒性。本研究调查了叶酸和FPGS在人类结肠癌细胞的化学治疗中的作用。检查叶酸缺乏对内源性FPGS水平的影响，以及改变的FPGS水平对化学敏感性的影响。叶酸缺乏降低了Caco2和HCT116人结肠癌细胞中FPGS的表达，并且仅在Caco2细胞中降低了FPGS的活性。建立了HCT116细胞中FPGS水平改变的体外模型，并描述了其生化特性。与反义hFPGS细胞相比，有义人FPGS cDNA赋予FPGS表达和活性上调，增加的细胞内叶酸浓度，增强的聚谷氨酸作用，增加的生长速率和对5-氟尿嘧啶的化学敏感性。总体而言，这些数据有助于当前对叶酸和FPGS在人类结肠癌细胞的化学治疗中的作用的了解。

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作者
Smirnakis, Francesca F.;
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作者单位

University of Toronto (Canada).;

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授予单位 University of Toronto (Canada).;
学科 Health Sciences Nutrition.;Health Sciences Oncology.
学位 M.Sc.
年度 2002
页码 153 p.
总页数 153
原文格式 PDF
正文语种 eng
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The role of folate and folylpoly-gamma-glutamate synthetase (FPGS) in the chemotherapeutics of human colon cancer cells.

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