Polyamine synthesis and transport inhibition in a human anaplastic thyroid carcinoma cell line in vitro and as xenograft tumors.
Polyamine synthesis and transport inhibition in a human anaplastic thyroid carcinoma cell line in vitro and as xenograft tumors.
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体外人类未变性甲状腺癌细胞系和异种移植肿瘤中的多胺合成和运输抑制。
DOI：
10.1089/thy.1999.9.805
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Ain,KB
中科院分区：
文献类型：
--
作者：
Yatin,M;Venkataraman,GM;Marcinek,R;Ain,KB
多胺是肿瘤转化和细胞增殖的基本细胞成分。由于多胺转运的补偿诱导，抑制多胺合成的抗肿瘤努力不足以诱导细胞毒性。用一种新的多聚精胺偶联物（聚精胺; PSpm）处理未分化的人甲状腺癌细胞系（DRO 90 -1），在低浓度下引起体外细胞毒性并抑制异种移植瘤的生长。Similarin vitrophilosophy的影响，注意到与其他两个人甲状腺未分化癌细胞系。这与抑制多胺的吸收和合成酶的活动，减少鸟氨酸脱羧酶（ODC）和S-腺苷甲硫氨酸脱羧酶（SAM-DC），但增加亚精胺/精胺N1-乙酰转移酶（SSAT）的活动，在DRO 90 -1细胞中测量。在随后使用这些细胞的研究中，PSpm在体外有效降低所有多胺的细胞内水平，导致细胞毒性，细胞外多胺不能逆转。低剂量的PSpm抑制体内肿瘤生长，但高剂量的PSpm增强异种移植瘤的生长。体内处理产生的PSpm降解产物可作为多胺生物合成的底物。这些研究表明，多胺代谢抑制是甲状腺未分化癌化疗的一个可行的靶点，尽管体内对PSpm的反应表明这种药物的临床应用有限。
Polyamines are essential cellular components for neoplastic transformation and cell proliferation. Antineoplastic efforts that inhibit polyamine synthesis are insufficient to induce cytotoxicity, due to compensatory induction of polyamine transport. Treatment of an anaplastic human thyroid carcinoma cell line (DRO90-1) with a novel polymeric spermine conjugate (polyspermine; PSpm) causedin vitrocytotoxicity and inhibited the growth of xenograft tumors at low concentrations. Similarin vitroantineoplastic effects were noted with two other human anaplastic thyroid carcinoma cell lines. This coincided with inhibition of polyamine uptake and synthetic enzyme activities, with reduced ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAM-DC) but increased spermidine/spermine N1-acetyltransferase (SSAT) activities, as measured in DRO90-1 cells. In subsequent studies using these cells, PSpm was effective in reducing the intracellular levels of all polyaminesin vitro, resulting in cytotoxicity that was not reversed by administration of extracellular polyamines. Low-dose PSpm inhibited tumor growthin vivo, but high doses of PSpm potentiated xenograft tumor growth. PSpm degradation products produced within vivotreatment may be produced that function as substrates for polyamine biosynthesis. These studies suggest that polyamine metabolism inhibition is a viable target for antineoplastic therapy of anaplastic thyroid carcinoma, although thein vivoresponse to PSpm suggests that this agent will have limited clinical utility.
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DOI：
10.1093/jnci/83.11.757
发表时间：
1991-06-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
MONKS, A;SCUDIERO, D;BOYD, M
通讯作者：
BOYD, M
α-二氟甲基鸟氨酸（鸟氨酸脱羧酶抑制剂）和 N1,N8-双（乙基）亚精胺（该酶的明显调节剂）对 L1210 细胞生长抑制的比较和表征。
影响因子：
11.2
作者：
Porter,CW;Ganis,B;Vinson,T;Marton,LJ;Kramer,DL;Bergeron,RJ
通讯作者：
Bergeron,RJ
抗酶介导的鸟氨酸脱羧酶合成的反馈抑制。
DOI：
10.1042/bj3200755
发表时间：
1996
期刊：
The Biochemical journal
影响因子：
--
作者：
Mitchell,JL;Choe,CY;Judd,GG
通讯作者：
Judd,GG
影响因子：
7.3
作者：
BERGERON, RJ;MCMANIS, JS;VINSON, JRT
通讯作者：
VINSON, JRT
影响因子：
11.2
作者：
Anthony E. Pegg
通讯作者：
Anthony E. Pegg