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亚硝基脲抗肿瘤化疗药物MCNU对五种人骨髓瘤细胞系的作用。

Effect of the nitrosourea anti-tumor chemotherapeutical agent MCNU on five human myeloma cell lines.

作者信息

Otsuki T, Sakaguchi H, Yamada O, Yawata Y, Ueki A

机构信息

Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.

出版信息

Oncol Rep. 1998 Jul-Aug;5(4):827-32. doi: 10.3892/or.5.4.827.

DOI:10.3892/or.5.4.827
PMID:9625826
Abstract

We investigated the effects of MCNU (methyl-6)3-(2-chloroethyl)-3-nitrosoureido)-6-deoxy- alpha-D-glucopyranoside), a nitrosourea anti-tumor agent developed in Japan, on cell growth and differentiation in five human myeloma cell lines and compared it with relative expression levels of MDR-1 gene. Although 10 microg/ml of MCNU inhibited cell growth in KMM-1 and KMS-5 lines, other three cell lines required 20-40 microg/ml of MCNU to obtain similar growth inhibition. Accumulation up to the G2 phase of the cell cycle was observed in KMM-1 and KMS-5 lines and the cloning efficiency of KMS-5 cells was reduced by MCNU. On the other hand, expression of surface markers on these lines was not altered remarkably except for increased expression of CD38 on KMS-5 cells. However, the effect of MCNU on these cell lines did not correlate to relative expression levels of MDR-1 gene analyzed by RT-PCR. MCNU may inhibit the growth of myeloma cells by the accumulation of these cells up to the G2 phase, but may not affect their differentiation.

摘要

我们研究了日本研发的亚硝基脲抗肿瘤药物MCNU(甲基-6)3-(2-氯乙基)-3-亚硝基脲基)-6-脱氧-α-D-吡喃葡萄糖苷)对五种人骨髓瘤细胞系细胞生长和分化的影响,并将其与MDR-1基因的相对表达水平进行了比较。尽管10微克/毫升的MCNU抑制了KMM-1和KMS-5细胞系的细胞生长,但其他三种细胞系需要20-40微克/毫升的MCNU才能获得类似的生长抑制效果。在KMM-1和KMS-5细胞系中观察到细胞周期积累至G2期,且MCNU降低了KMS-5细胞的克隆效率。另一方面,除了KMS-5细胞上CD38表达增加外,这些细胞系表面标志物的表达没有明显改变。然而,MCNU对这些细胞系的作用与通过逆转录聚合酶链反应分析的MDR-1基因的相对表达水平无关。MCNU可能通过使这些细胞积累至G2期来抑制骨髓瘤细胞的生长,但可能不影响其分化。

相似文献

1
Effect of the nitrosourea anti-tumor chemotherapeutical agent MCNU on five human myeloma cell lines.亚硝基脲抗肿瘤化疗药物MCNU对五种人骨髓瘤细胞系的作用。
Oncol Rep. 1998 Jul-Aug;5(4):827-32. doi: 10.3892/or.5.4.827.
2
[Phase II study with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].
Gan To Kagaku Ryoho. 1985 Jun;12(6):1253-9.
3
Antitumor activity and toxicity of methyl 6-[3-(2-chloroethyl)- 3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside in experimental animals.6-[3-(2-氯乙基)-3-亚硝基脲基]-6-脱氧-α-D-吡喃葡萄糖苷甲酯在实验动物中的抗肿瘤活性与毒性
Gan. 1984 Oct;75(10):937-46.
4
[Effect of MCNU on growth kinetics of human plasma cell lines--in comparison with melphalan].
Nihon Ketsueki Gakkai Zasshi. 1987 Aug;50(5):971-7.
5
[Phase II study of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU)].
Gan To Kagaku Ryoho. 1985 Mar;12(3 Pt 1):493-8.
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Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in dogs.犬脑室-腰椎灌注6-[3-(2-氯乙基)-3-亚硝基脲基]-6-脱氧-α-D-吡喃葡萄糖苷(MCNU)的神经毒性和药代动力学
J Neurooncol. 1994;19(3):239-44. doi: 10.1007/BF01053277.
7
Beneficial treatment with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside in a patient with primary myelofibrosis.
Acta Haematol. 1991;85(2):103-4. doi: 10.1159/000204866.
8
Biologic activity of MCNU: a new antitumor agent.新型抗肿瘤药物甲环亚硝脲(MCNU)的生物学活性
Cancer Treat Rep. 1979 Jun;63(6):961-70.
9
[Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].
Gan To Kagaku Ryoho. 1983 Jun;10(6):1518-23.
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A new nitrosourea derivative for the treatment of chronic myelogenous leukemia.
Leuk Res. 1988;12(6):487-90. doi: 10.1016/0145-2126(88)90115-4.

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