The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells.
The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells.
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DOI：
10.1016/j.fertnstert.2008.11.018
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发表时间：
2010-03-01
影响因子：
6.7
通讯作者：
Nowak RA
中科院分区：
文献类型：
--
作者：
Grudzien MM;Low PS;Manning PC;Arredondo M;Belton RJ Jr;Nowak RA
探讨抗纤维化药物常山酮对体外培养的子宫肌层和平滑肌瘤平滑肌细胞的细胞外基质生成、细胞增殖和凋亡的影响。对比和对照实验研究。大学研究实验室。在选择性子宫切除术时，从8名不同患者中获得平滑肌瘤和子宫肌层组织。通过氚化胸苷摄取试验和细胞计数试验评估常山酮对细胞增殖的影响。通过实时定量PCR评估对TGFβ1、I型胶原和III型胶原mRNA水平的影响。使用荧光测定法测定对凋亡的影响，以测量半胱天冬酶3和7的变化。常山酮通过在24小时内抑制DNA合成并随后在48-72小时诱导细胞凋亡（通过增加的半胱天冬酶3/7测量），以剂量依赖性方式抑制平滑肌瘤和自体子宫肌层细胞的细胞增殖。常山酮还显著降低两种细胞类型中I型胶原（α1）和III型胶原（α1）mRNA水平，以及促纤维化因子TGFβ1 mRNA水平。这些结果提供了证据，支持使用抗纤维化药物常山酮作为一种新的药物治疗子宫肌瘤。
To investigate the effects of the antifibrotic drug halofuginone on extracellular matrix production, cell proliferation and apoptosis of cultured myometrial and leiomyoma smooth muscle cells. Comparative and controlled experimental research study. University research laboratory. Leiomyoma and myometrial tissues were obtained from 8 different patients at the time of elective hysterectomy. The effects of halofuginone on cell proliferation were assessed by tritiated thymidine uptake assays and cell count assays. Effects on TGFβ1, collagen type I, and collagen type III mRNA levels were assessed by quantitative real-time PCR. Effects on apoptosis were assayed using a chemiluminescent assay to measure changes in caspase 3 and 7. Halofuginone inhibited cell proliferation of both leiomyoma and autologous myometrial cells in a dose-dependent manner by inhibiting DNA synthesis within 24 hrs and later inducing apoptosis (as measured by increased caspase 3/7) by 48-72 hrs. Halofuginone also significantly reduced collagen type I (α1) and collagen type III (α1) mRNA levels, as well as the profibrotic factor TGFβ1 mRNA levels in both cell types. These results provide evidence to support the use of the antifibrotic drug halofuginone as a novel drug treatment for uterine leiomyomas.
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DOI：
10.1073/pnas.170290997
发表时间：
2000-08-29
影响因子：
11.1
作者：
Henriet, P;Zhong, ZD;DeClerck, YA
通讯作者：
DeClerck, YA
影响因子：
2.8
作者：
Gavish, Z;Pinthus, FH;Pines, M
通讯作者：
Pines, M
影响因子：
8.4
作者：
Nagler, A;Ohana, M;Ilan, Y
通讯作者：
Ilan, Y
影响因子：
5.8
作者：
Lee, BS;Nowak, RA
通讯作者：
Nowak, RA
影响因子：
4.8
作者：
Popov, Yury;Patsenker, Eleonora;Schuppan, Detlef
通讯作者：
Schuppan, Detlef