Nowak R A
Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School and the Center for Uterine Fibroids, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Environ Health Perspect. 2000 Oct;108 Suppl 5:849-53. doi: 10.1289/ehp.00108s5849.
Leiomyomas (fibroids) are benign smooth-muscle cell (SMC) tumors of the uterus and are the most common pelvic tumors in women. These tumors occur primarily during the reproductive years and are the most common indication for hysterectomy in women. Unfortunately the only effective treatments for leiomyomas and the associated abnormal uterine bleeding are surgical, involving either hysterectomy, myomectomy, or hysteroscopic removal of the tumors. The goal of this paper is to discuss recent research findings that support the idea of using therapeutic compounds that block the actions of specific growth factors as therapeutic agents for treatment of leiomyomas and abnormal uterine bleeding. Most of the studies were carried out using cell cultures of leiomyoma or myometrial SMCs. Primary cultures of SMCs provide a system for investigation of the roles of growth factors and their receptors in proliferation of normal myometrial and leiomyoma SMCs. Several growth factors have been shown to be present and to have regulatory roles in the proliferation of uterine SMCs. Bioassay and Western blotting of fast protein liquid chromatography fractions of tissue extracts identified platelet-derived growth factor, heparin-binding epidermal growth factor, hepatoma-derived growth factor, and basic fibroblast growth factor in normal myometrium and fibroid tumors. The presence of heparin-binding growth factors suggests a possible focus for therapeutic agents. RG13577 (a heparinlike compound) and halofuginone (an alkyloid) reversibly inhibited DNA synthesis of normal myometrial and leiomyoma cells without toxic effects. Pirfenidone, a known antifibrotic drug, inhibited DNA synthesis and synthesis of collagen type I mRNA in normal and fibroid cells, and decreased collagen type III mRNA only in normal myometrial cells. Another hopeful therapeutic candidate, interferon-Alpha, significantly inhibited growth factor-stimulated proliferation in both normal and leiomyoma cells. These results suggest that future nonsurgical treatments for leiomyomas may include compounds that block the actions of specific growth factors that regulate proliferation and collagen production by uterine SMCs.
平滑肌瘤（纤维瘤）是子宫的良性平滑肌细胞（SMC）肿瘤，是女性最常见的盆腔肿瘤。这些肿瘤主要发生在生育年龄，是女性子宫切除术最常见的指征。不幸的是，平滑肌瘤及相关异常子宫出血的唯一有效治疗方法是手术，包括子宫切除术、肌瘤切除术或宫腔镜下肿瘤切除术。本文的目的是讨论最近的研究结果，这些结果支持使用能阻断特定生长因子作用的治疗性化合物作为治疗平滑肌瘤和异常子宫出血的治疗药物的观点。大多数研究是使用平滑肌瘤或子宫肌层SMC的细胞培养物进行的。SMC的原代培养为研究生长因子及其受体在正常子宫肌层和平滑肌瘤SMC增殖中的作用提供了一个系统。已证明几种生长因子存在于子宫SMC增殖中并具有调节作用。对组织提取物的快速蛋白质液相色谱馏分进行生物测定和蛋白质印迹分析，在正常子宫肌层和肌瘤肿瘤中鉴定出血小板衍生生长因子、肝素结合表皮生长因子、肝癌衍生生长因子和碱性成纤维细胞生长因子。肝素结合生长因子的存在提示了治疗药物的一个可能靶点。RG13577（一种类肝素化合物）和常山酮（一种生物碱）可逆地抑制正常子宫肌层和平滑肌瘤细胞的DNA合成，且无毒性作用。已知的抗纤维化药物吡非尼酮抑制正常和平滑肌瘤细胞中的DNA合成及I型胶原mRNA的合成，且仅在正常子宫肌层细胞中降低III型胶原mRNA水平。另一种有希望的治疗候选药物α干扰素显著抑制正常和平滑肌瘤细胞中生长因子刺激的增殖。这些结果表明，未来平滑肌瘤的非手术治疗可能包括能阻断调节子宫SMC增殖和胶原产生的特定生长因子作用的化合物。
