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糖皮质激素对人平滑肌肉瘤细胞系SK-LMS-1生长的影响。

The influence of glucocorticoids on the growth of a human leiomyosarcoma cell line SK-LMS-1.

作者信息

Madsen W E, Gupta T K, Walker M J

机构信息

Department of Surgery, University of Illinois College of Medicine, Cook County Hospital, Chicago.

出版信息

Int J Cancer. 1989 Dec 15;44(6):1034-40. doi: 10.1002/ijc.2910440616.

Abstract

A cell line derived from a human leiomyosarcoma, SK-LMS-I, has cystolic [Bmax 201.6 +/- 39.7, means +/- SD, fm/mg cytosol protein KD 14.6 +/- 7.8 nM (n = 8)] and nuclear [Bmax 189.2 +/- 87.3 fM/mg DNA, KD 4.8 +/- 0.26 nM (n = 5)] glucocorticoid receptor, by Scatchard analysis of tumors grown in male athymic mice. Tumor growth of SK-LMS-I cells in male athymic mice is inhibited by daily s.c. injection of DEX 5 micrograms, DEX 25 micrograms, DEX 5 micrograms with 5 mu RU-486 and 5 micrograms RU-486. In sharp contrast, in vitro, glucocorticoid markedly stimulates the growth (as determined by cell number) of SK-LMS-I cells, principally at higher cell densities (days 10-21 of growth carried on over a 21- to 23-day period), the greatest stimulation being seen with DEX 10(-6) to 10(-8) M, and no stimulation being seen with DEX 10(-9) and 10(-10) M. In vitro, glucocorticoids with higher affinity for the GR stimulate growth, steroids with lower affinity inhibit growth. No alterations in cell-cycle distribution (percent G0/G1, S, or G2/m) could be found by flow cytometric analysis of glucocorticoid-stimulated asynchronously growing cultures. Single, isolated, untreated SK-LMS-I cells form colonies in soft agar with an efficiency of 1.78 +/- 0.10%. Pre-treatment of cells with DEX 10(-7) M increases this to 3.24 +/- 0.17%, while cells pre-treated with both DEX 10(-7) M RU-486 10(7) M form colonies with the same efficiency as untreated cells. Glucocorticoids have inhibitory effects on in vivo growth and stimulatory effects on in vitro growth of a GR-positive human leiomyosarcoma cell line.

摘要

通过对在雄性无胸腺小鼠体内生长的肿瘤进行Scatchard分析,源自人平滑肌肉瘤的细胞系SK-LMS-I具有胞质糖皮质激素受体[Bmax 201.6±39.7,平均值±标准差,fm/mg胞质溶胶蛋白,KD 14.6±7.8 nM(n = 8)]和核糖皮质激素受体[Bmax 189.2±87.3 fM/mg DNA,KD 4.8±0.26 nM(n = 5)]。雄性无胸腺小鼠体内SK-LMS-I细胞的肿瘤生长受到每日皮下注射5微克地塞米松、25微克地塞米松、5微克地塞米松与5微摩尔RU-486以及5微克RU-486的抑制。与之形成鲜明对比的是,在体外,糖皮质激素显著刺激SK-LMS-I细胞的生长(通过细胞数量测定),主要是在较高细胞密度时(在21至23天的时间段内生长10至21天),最大刺激作用出现在10⁻⁶至10⁻⁸M的地塞米松时,而10⁻⁹和10⁻¹⁰M的地塞米松则未观察到刺激作用。在体外,对糖皮质激素受体具有较高亲和力的糖皮质激素刺激生长,而亲和力较低的类固醇则抑制生长。通过对糖皮质激素刺激的异步生长培养物进行流式细胞术分析,未发现细胞周期分布(G0/G1、S或G2/M期百分比)有改变。单个、分离的未处理SK-LMS-I细胞在软琼脂中形成集落的效率为1.78±0.10%。用10⁻⁷M地塞米松预处理细胞可将此效率提高至3.24±0.17%,而用10⁻⁷M地塞米松和10⁻⁷M RU-486预处理的细胞形成集落的效率与未处理细胞相同。糖皮质激素对GR阳性的人平滑肌肉瘤细胞系的体内生长具有抑制作用,对体外生长具有刺激作用。

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