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[多胺生物合成抑制剂DFMO对裸鼠移植人结肠癌生长的抑制作用]

[Inhibition by polyamine biosynthesis inhibitor DFMO of the growth of transplanted human colon cancer in nude mice].

作者信息

Wang M

机构信息

Cancer Institute, Zhejiang Medical University, Hangzhou.

出版信息

Zhonghua Zhong Liu Za Zhi. 1991 Sep;13(5):335-7.

PMID:1782843
Abstract

A human colon cancer cell line Hce-8693 was heterotransplanted in nude mice. polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) showed a marked reproducible inhibition in this model. The size and weight of transplanted tumor in DFMO group were smaller than those of the control group and the average inhibition rate was 72.8% (P less than 0.001). DFMO showed higher tumor inhibitory rate than 5-Fu (35.4%) (P less than 0.001). Furthermore, DFMO demonstrated less severe bone marrow inhibition in the nude mice than 5-Fu (20.0% vs 53.2%, P less than 0.001). There was no synergistic action in these two drugs at the experimental doses. The concentration of putrescine and spermidine in the serum and tumor tissue in the DFMO group were 70% lower than those of the control group (P less than 0.001). These results indicate that the anti-tumor effect of DFMO might be explained by the inhibition of polyamine biosynthesis and this study provides an experimental basis for future clinical application of DFMO.

摘要

将人结肠癌细胞系Hce - 8693异种移植到裸鼠体内。多胺生物合成抑制剂α - 二氟甲基鸟氨酸(DFMO)在该模型中显示出显著且可重复的抑制作用。DFMO组移植瘤的大小和重量均小于对照组,平均抑制率为72.8%(P < 0.001)。DFMO的肿瘤抑制率高于5 - 氟尿嘧啶(5 - Fu,35.4%)(P < 0.001)。此外,DFMO对裸鼠骨髓的抑制作用比5 - Fu轻(20.0%对53.2%,P < 0.001)。在实验剂量下,这两种药物没有协同作用。DFMO组血清和肿瘤组织中腐胺和亚精胺的浓度比对照组低70%(P < 0.001)。这些结果表明,DFMO的抗肿瘤作用可能是通过抑制多胺生物合成来解释的,本研究为DFMO未来的临床应用提供了实验依据。

相似文献

1
[Inhibition by polyamine biosynthesis inhibitor DFMO of the growth of transplanted human colon cancer in nude mice].[多胺生物合成抑制剂DFMO对裸鼠移植人结肠癌生长的抑制作用]
Zhonghua Zhong Liu Za Zhi. 1991 Sep;13(5):335-7.
2
Antimetastatic activity of DL-alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, in mice.多胺生物合成抑制剂DL-α-二氟甲基鸟氨酸在小鼠体内的抗转移活性
Cancer Res. 1987 Feb 15;47(4):933-5.
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Reduced growth rate of dimethylhydrazine-induced colon tumors in rats.二甲基肼诱导的大鼠结肠肿瘤生长速率降低
Cancer Res. 1992 Feb 1;52(3):696-700.
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[Antitumor effect of alpha-difluoromethylornithine (DFMO) changes in ornithine decarboxylase (ODC) activity and polyamine (PA) levels in human tumor transplanted into nude mice].[α-二氟甲基鸟氨酸(DFMO)对移植到裸鼠体内的人肿瘤中鸟氨酸脱羧酶(ODC)活性和多胺(PA)水平的影响及抗肿瘤作用]
Nihon Geka Gakkai Zasshi. 1989 May;90(5):650-60.
5
Effects of alpha-difluoromethylornithine and 5-fluorouracil on the proliferation of a human colon adenocarcinoma cell line.α-二氟甲基鸟氨酸和5-氟尿嘧啶对人结肠腺癌细胞系增殖的影响。
Cancer Res. 1983 Sep;43(9):4035-8.
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Long-term maintenance therapy of established human small cell variant lung carcinoma implants in athymic mice with a cyclic regimen of difluoromethylornithine.用二氟甲基鸟氨酸的循环方案对无胸腺小鼠体内已建立的人小细胞变异型肺癌植入物进行长期维持治疗。
Cancer Res. 1986 Apr;46(4 Pt 1):1849-53.
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Effects of alpha-difluoromethylornithine and recombinant interferon-alpha 2 on the growth of a human renal cell adenocarcinoma xenograft in nude mice.α-二氟甲基鸟氨酸与重组干扰素α-2对人肾细胞腺癌裸鼠移植瘤生长的影响。
Cancer Res. 1984 Aug;44(8):3220-5.
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Successful treatment with DL-alpha-difluoromethylornithine in established human small cell variant lung carcinoma implants in athymic mice.DL-α-二氟甲基鸟氨酸成功治疗无胸腺小鼠体内已形成的人小细胞变异型肺癌植入瘤。
Cancer Res. 1983 Sep;43(9):4239-43.
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Novel lysine-spermine conjugate inhibits polyamine transport and inhibits cell growth when given with DFMO.新型赖氨酸-精胺共轭物抑制多胺转运,并在与二氟甲基鸟氨酸联合使用时抑制细胞生长。
Exp Cell Res. 2000 Nov 25;261(1):293-302. doi: 10.1006/excr.2000.5033.
10
In vivo growth inhibition of human colon carcinoma cells (HT-29) by all-trans-retinoic acid, difluoromethylornithine, and colon mitosis inhibitor, individually and in combination.全反式维甲酸、二氟甲基鸟氨酸和结肠有丝分裂抑制剂单独及联合使用对人结肠癌细胞(HT - 29)的体内生长抑制作用。
Anticancer Res. 2000 Sep-Oct;20(5B):3485-9.

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