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胰腺癌和结肠癌在体内对环孢素和α-二氟甲基鸟氨酸的敏感性差异

Differential sensitivity of pancreatic and colon cancer to cyclosporine and alpha-difluoromethylornithine in vivo.

作者信息

Saydjari R, Townsend C M, Barranco S C, Thompson J C

机构信息

Department of Surgery, University of Texas Medical Branch, Galveston.

出版信息

Invest New Drugs. 1988 Dec;6(4):265-72. doi: 10.1007/BF00173644.

DOI:10.1007/BF00173644
PMID:3147968
Abstract

We have previously reported that the in vitro growth of MC-26 mouse colon cancer and H2T hamster pancreatic cancer cells are inhibited by cyclosporine (CsA) and alpha-difluoromethylornithine (DFMO). The present study was designed to investigate the effects of these two drugs on the two experimental tumors (MC-26 and H2T) growing in vivo. Forty-eight male Balb/c mice or Syrian golden hamsters were inoculated with MC-26 (250,000) or H2T (500,000) cells, respectively, and then were randomized into four groups of 12 each: group I was control; group II received CsA; group III received DFMO; group IV received a combination of CsA and DFMO. MC-26 tumors were significantly more sensitive than H2T tumors to the effects of CsA and DFMO. MC-26 tumor growth and tumor weight, as well as the tumor content of DNA, RNA, and protein were all significantly more reduced by CsA and DFMO than were the H2T tumors. Our present study shows that both CsA and DFMO are potent inhibitors of MC-26 colon carcinoma growth in vivo, though DFMO is more than twice as effective as CsA. DFMO also produced greater reductions in the tumor content of DNA, RNA, and protein than did CsA. DFMO significantly decreased the concentrations of polyamines in both H2T and MC-26 tumors; the MC-26 tumors were affected to a greater degree.

摘要

我们之前曾报道,环孢素(CsA)和α-二氟甲基鸟氨酸(DFMO)可抑制MC-26小鼠结肠癌和H2T仓鼠胰腺癌细胞的体外生长。本研究旨在调查这两种药物对两种体内生长的实验性肿瘤(MC-26和H2T)的影响。48只雄性Balb/c小鼠或叙利亚金仓鼠分别接种MC-26(250,000个)或H2T(500,000个)细胞,然后随机分为四组,每组12只:第一组为对照组;第二组接受CsA;第三组接受DFMO;第四组接受CsA和DFMO联合治疗。MC-26肿瘤对CsA和DFMO的作用比H2T肿瘤更敏感。与H2T肿瘤相比,CsA和DFMO对MC-26肿瘤生长、肿瘤重量以及肿瘤中DNA、RNA和蛋白质含量的降低幅度均更大。我们目前的研究表明,CsA和DFMO都是体内MC-26结肠癌生长的有效抑制剂,尽管DFMO的效果是CsA的两倍多。DFMO对肿瘤中DNA、RNA和蛋白质含量的降低幅度也比CsA更大。DFMO显著降低了H2T和MC-26肿瘤中多胺的浓度;MC-26肿瘤受到的影响更大。

相似文献

1
Differential sensitivity of pancreatic and colon cancer to cyclosporine and alpha-difluoromethylornithine in vivo.胰腺癌和结肠癌在体内对环孢素和α-二氟甲基鸟氨酸的敏感性差异
Invest New Drugs. 1988 Dec;6(4):265-72. doi: 10.1007/BF00173644.
2
Cyclosporine and alpha-difluoromethylornithine exhibit differential effects on colon and pancreatic cancer in vitro.环孢素和α-二氟甲基鸟氨酸在体外对结肠癌和胰腺癌表现出不同的作用。
Invest New Drugs. 1987;5(3):251-8. doi: 10.1007/BF00175295.
3
Treatment of hamster pancreatic cancer with alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis.用α-二氟甲基鸟氨酸(一种多胺生物合成抑制剂)治疗仓鼠胰腺癌。
J Natl Cancer Inst. 1987 Sep;79(3):543-8.
4
2-Deoxy-D-glucose inhibits the antitumor effects of alpha-difluoromethylornithine on the growth of colon cancer in vivo.2-脱氧-D-葡萄糖抑制α-二氟甲基鸟氨酸对体内结肠癌生长的抗肿瘤作用。
Invest New Drugs. 1989 Jul;7(2-3):131-8. doi: 10.1007/BF00170849.
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Effects of cyclosporin A and alpha-difluoromethylornithine on the growth of hamster pancreatic cancer in vitro.环孢素A和α-二氟甲基鸟氨酸对仓鼠胰腺癌体外生长的影响。
J Natl Cancer Inst. 1986 Nov;77(5):1087-92.
6
The effects of 2-deoxy-D-glucose and alpha-difluoromethylornithine on the growth of pancreatic cancer in vivo.2-脱氧-D-葡萄糖和α-二氟甲基鸟氨酸对胰腺癌体内生长的影响。
Pancreas. 1989;4(1):38-43. doi: 10.1097/00006676-198902000-00006.
7
Effects of cyclosporine and alpha-difluoromethylornithine on the growth of mouse colon cancer in vitro.环孢素和α-二氟甲基鸟氨酸对小鼠结肠癌体外生长的影响。
Life Sci. 1987 Jan 26;40(4):359-66. doi: 10.1016/0024-3205(87)90137-8.
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Differential sensitivity of various human tumors to inhibition of polyamine biosynthesis in vivo.多种人类肿瘤在体内对多胺生物合成抑制的差异敏感性。
Int J Cancer. 1991 Jan 2;47(1):44-8. doi: 10.1002/ijc.2910470109.
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Cortivazol increases glucocorticoid receptor expression and inhibits growth of hamster pancreatic cancer (H2T) in vivo.可替伐唑可增加糖皮质激素受体表达,并在体内抑制仓鼠胰腺癌(H2T)的生长。
Pancreas. 1993 Jan;8(1):7-14. doi: 10.1097/00006676-199301000-00004.
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Alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, augments cyclosporin A inhibition of cytolytic T lymphocyte induction.α-二氟甲基鸟氨酸,一种多胺生物合成抑制剂,增强环孢素A对细胞毒性T淋巴细胞诱导的抑制作用。
Clin Exp Immunol. 1989 Jul;77(1):151-6.

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Jpn J Cancer Res. 1994 Jul;85(7):704-9. doi: 10.1111/j.1349-7006.1994.tb02418.x.
2
Purification of a new galactanase from Penicillium oxalicum catalysing the hydrolysis of beta-(1----5)-galactofuran linkages.从草酸青霉中纯化一种新型半乳聚糖酶,该酶催化β-(1→5)-半乳呋喃糖苷键的水解。
Biochem J. 1992 Feb 1;281 ( Pt 3)(Pt 3):657-60. doi: 10.1042/bj2810657.

本文引用的文献

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The nucleic acids of plant tissues; the extraction and estimation of desoxypentose nucleic acid and pentose nucleic acid.植物组织的核酸;脱氧戊糖核酸和戊糖核酸的提取与测定
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Uptake and nature of the intracellular binding of cyclosporin A in a murine thymoma cell line, BW5147.环孢菌素A在小鼠胸腺瘤细胞系BW5147中的细胞内结合摄取及性质
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Chemotherapeutic implications of polyamine biosynthesis inhibition.多胺生物合成抑制的化疗意义。
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The physiology and biochemistry of polyamines in plants.植物中多胺的生理生化特性
Arch Biochem Biophys. 1984 Dec;235(2):283-303. doi: 10.1016/0003-9861(84)90201-7.