子宫肌瘤发生机制及相关治疗研究进展

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (2): 140-146.

子宫肌瘤发生机制及相关治疗研究进展

刘林燕¹, 袁胜涛², 余伯阳¹

¹中国药科大学中药复方研究室, ²中国药科大学新药筛选中心, 南京 210038, 江苏

收稿日期:2006-12-11 修回日期:2007-01-20 出版日期:2007-02-26 发布日期:2020-10-27
通讯作者: 余伯阳, 男, 教授, 博士生导师, 主要从事中药和天然药物领域的基础和应用研究。Tel:025-85391042 　E-mail:boyangyu59@163.com
作者简介:刘林燕, 女, 硕士在读。Tel:13770830525 　E-mail:linyanliu@hotmail.com
基金资助:
国家“十五” 重大专项(2002AA2Z343E); 国家“十五” 滚动项目(2004AA2Z3785); 江苏省药效研究和评价服务中心课题(BM2005103)

Overview and research progress of tumorigenesis and related therapies of Uterine leiomyomas

LIU Lin-yan¹, YUAN Sheng-tao², YU Bo-yang¹

¹Department of Chinese Medicinal Prescription, China Pharmaceutical University, Nanjing 210038, Jiangsu, China;
²Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210038, Jiangsu, China

Received:2006-12-11 Revised:2007-01-20 Online:2007-02-26 Published:2020-10-27

摘要/Abstract

摘要： 子宫肌瘤是妇科常见的良性肿瘤, 迄今为止发病机制不明且无理想的治疗药物。本文综述了近几年来子宫肌瘤的发生机制及相关治疗研究进展,包括基因、激素、生长因子及其它主要旁路, 为寻找出新的更为确切的研究方法、开发出疗效好副作用小的抗子宫肌瘤药物提供参考。

关键词: 子宫肌瘤, 机制, 治疗

Abstract: Uterine leiomyomas, also called fibroids, are the most common reproductive tract neoplasm in premenopausal women.The discovery and development of medicinal therapies for uterine leiomyoma have been hampered by a lack of understanding in terms of the etiology and molecular mechanisms underlying the development of these lesions.As a reference, this article reviews mechanisms of the tumorigenesis and medicinal therapies, including genes, hormones, growth factors and some other pathways, in order to understand the tumor well and find more promising new drugs.

Key words: uterine leiomyoma, mechanisms, therapy

中图分类号:

R711.74

刘林燕, 袁胜涛, 余伯阳. 子宫肌瘤发生机制及相关治疗研究进展[J]. 中国临床药理学与治疗学, 2007, 12(2): 140-146.

LIU Lin-yan, YUAN Sheng-tao, YU Bo-yang. Overview and research progress of tumorigenesis and related therapies of Uterine leiomyomas[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(2): 140-146.

参考文献

[1] Walker CL, Stewart EA.Uterine Fibroids:The Elephant in the Room[J]. Science, 2005;10:1589-1592.
[2] Baysal BE.Krebs cycle enzymes as tumor suppressors[J]. Drug Discov Today, 2005;2:247-254.
[3] Cook JD, Walker CL.Treatment strategies for uterine leiomyoma: the role of hormonal modulation[J]. Semin Reprod Med,2004;22:105-111.
[4] Barbarisi A, Petillo O, Di Lieto A, et al. 17β-estradiol elicits an autocrine leiomyoma cell proliferation:evidence for a stimulation of protein kinase-dependent pathway[J]. J Cell Physiol,2001;186:414-424.
[5] Maruo T, Ohara N, Wang J, et al. Sex steroidal regulation of uterine leiomyoma growth and apoptosis[J]. Hum Reprod Update, 2004;10:207-220.
[6] Swartz CD, Afshari CA, Yu L, et al. Estrogen-induced changes in IGF-I, Myb family andMAP kinase pathway genes in human uterine leiomyoma and normal uterine smooth muscle cell lines[J]. Mol Hum Reprod, 2005;11:441-450.
[7] Kasai T, ShozuM, Murakami K, et al. Increased expression of type I 17beta-hydroxysteroid dehydrogenase enhances in situ production of estradiol in uterine leiomyoma[J]. J Clin EndocrinolMetab, 2004;89:5661-5668.
[8] Al-Hendy A, Salama SA.Catechol-O-methyltransferase polymorphism is associated with increased uterine leiomyoma risk in different ethnic groups[J]. J Soc Gynecol Investig, 2006;13:136-144.
[9] Schultze-Mosgau A, Griesinger G, Altgassen C, et al. New developments in the use of peptide gonadotropin-releasing hormone antagonists versus agonists[J]. Expert Opin Investig Drugs,2005;14:1085-1097.
[10] Hummel CW, Geiser AG, Bryant HU, et al. A selective estrogen receptor modulator designed for the treatment of uterine leiomyoma with unique tissue specificity for uterus and ovaries in rats[J]. J Med Chem, 2005;48:6772-6775.
[11] DeManno D, Elger W, Garg R, et al. Asoprisnil (J867):a selective progesterone receptor modulator for gynecological therapy[J]. Steroids, 2003;68:1019-1032.
[12] ChenW, Ohara N, Wang J, et al. A novel selective progesterone receptor modulator asoprisnil (J867) inhibits proliferation and induces apoptosis in cultured human uterine leiomyoma cells in the absence of comparable effects on myometrial cells[J]. J Clin Endocrinol Metab, 2006;91:1296-1304.
[13] Wang J, Ohara N, Wang Z, et al. A novel selective progester- one receptor modulator asoprisnil (J867) down-regulates the expression of EGF, IGF-I, TGF {beta}3 and their receptors in cultured uterine leiomyoma cells[J]. Hum Reprod, 2006;21:1869-1877.
[14] Al-Hendy A.Gene Therapy of uterine fibroids:adenovirus-mediated expression of dominant negative estrogen receptor inhibits ERE-reporter transactivation in rat and human leiomyoma cells[J]. Mol Ther, 2005;11:S213.
[15] Sumitani H, Shozu M, Segawa T, et al. In situ estrogen synthesized by aromatase P450 in uterine leiomyoma cells promotes cell growth probably via an autocrine intracrine mechanism[J]. Endocrinology, 2000;141:3852-3861.
[16] Shozu M, Murakami K, Segawa T, et al. Successful treatment of a symptomatic uterine leiomyoma in a perimenopausalwoman with a nonsteroidal aromatase inhibitor[J]. Fertil Steril, 2003; 79:628-629.
[17] Luo X, Ding L, Xu J, et al. Gene expression profiling of leiomyoma and myometrial smooth muscle cells in response to transforming growth factor-beta[J]. Endocrinology, 2005;146:1097-1118.
[18] WolanskaM, Bankowski E.Fibroblast growth factors (FGF) in human myometrium and uterine leiomyomas in various stages of tumour growth[J]. Biochimie, 2006;88:141-146.
[19] Nowak RA.Novel therapeutic strategies for leiomyomas:targeting growth factors and their receptors[J]. Environ Health Perspect, 2000;108(Suppl 5):849-853.
[20] Shushan A, Rojansky N, Laufer N, et al. The AG1478 tyrosine kinase inhibitor is an effective suppressor of leiomyoma cell growth[J]. Hum Reprod, 2004;19:1957-1967.
[21] Niu H, Simari RD, Zimmermann EM, et al. Nonviral vectormediated thymidine kinase gene transfer and ganciclovir treatment in leiomyoma cells[J]. Obstet Gynecol, 1998;91:735-740.
[22] Al-Hendy A, Kamel M, Christman G, et al. Uterine fibroids gene therapy:adenovirus-mediated herpes simplex virus thymidine kinase ganciclovir treatment inhibits growth of human and rat leiomyoma cells[J]. Mol Ther, 2005;11:S102.
[23] Gamage SD, Bischoff ED, Burroughs KD, et al. Efficacy of LGD1069 (Targretin), a retinoid X receptor-selective ligand, for treatment of uterine leiomyoma[J]. J Pharmacol Exp Ther, 2000;295:677-681.
[24] Adolfsson PI, Haug I, Berg G, et al. Changes in beta(2)-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas[J]. Mol Hum Reprod, 2000;6:835-842.
[25] Houston KD, Copland JA, Broaddus RR, et al. Inhibition of proliferation and estrogen receptor signaling by peroxisome proliferator-activated receptor-ligands in uterine leiomyoma1[J]. Cancer Res, 2003;63:1221-1227.
[26] Kim BY, Cho CH, Song DK, et al. Ciglitizone inhibits cell proliferation in human uterine leiomyoma via activation of storeoperated Ca²+ channels[J]. Am J Phy siol Cell Physiol, 2005; 88:C389-C395.
[27] Loy CJ, Evelyn S, Lim FK, et al. Growth dynamics of human leiomyoma cells and inhibitory effects of the peroxisome proliferator-activated receptor-gamma ligand, pioglitazone[J]. Mol Hum Reprod, 2005;1:561-566.
[28] Nowak RA.Drug therapies for uterine fibroids:a new approach to an old problem[J]. Drug Discovery Today:Therapeutic Strategies, 2004;1:237-242.