整合素avβ3单克隆抗体对小鼠子宫内膜异位病灶的抑制作用

南方医科大学学报 ›› 2005, Vol. 25 ›› Issue (06): 709-711.

整合素avβ3单克隆抗体对小鼠子宫内膜异位病灶的抑制作用

赵军¹, 宗利丽², 李亚里¹

1. 解放军总医院妇产科, 北京, 100853;
2. 南方医科大学珠江医院妇产科, 广东, 广州, 510282

出版日期:2005-06-20 发布日期:2005-06-20
基金资助:
收稿日期:2005-1-2。
基金项目:国家自然科学基金(3983035)
作者简介:赵军(1974- ),女,解放军总医院在读硕士研究生,研究方向:子宫内膜异位症,电话:010-63822024
通讯作者:李亚里,北京解放军总医院妇产科,电话:010-66939292

Inhibitory effects of integrin avβ3 monoclonal antibody on implanted lesions of endometriosis model of SCID mouse

ZHAO Jun¹, ZONG Li-li², LI Ya-li¹

1. 解放军总医院妇产科, 北京, 100853;
2. 南方医科大学珠江医院妇产科, 广东, 广州, 510282

Online:2005-06-20 Published:2005-06-20

摘要/Abstract

摘要： 目的研究整合素avβ3单克隆抗体对SCID小鼠子宫内膜异位病灶生长和微血管形成的影响。方法建立人子宫内膜异位症小鼠皮下移植病灶模型。治疗组尾静脉注射整合素avβ3单克隆抗体Lm609(250μg/只),对照组给予相应体积的PBS,1周2次。4周后处死动物,测量病灶,采用免疫组化法检测病灶微血管密度(MVD)及整合素avβ3的表达。结果治疗组与对照组皮下移植病灶质量分别为(0.82±0.09)g和(0.51±0.93)g(P<0.05),病灶组织中MVD则分别为31.2±4.4和14.4±1.8(P<0.05),治疗组病灶受到显著抑制。结论整合素avβ3单克隆抗体通过抑制微血管形成而抑制子宫内膜异位病灶的生长。

Abstract: Objective To explore the potential use of integrin avβ3 (Lm609) monoclonal antibody against ectopic lesion and microvessel angiogenesis of human endometriosis xenografts in SCID mice. Methods The endometrial tissues from endometriosis patients were inoculated subcutaneously into SCID mouse, which were treated with Lm609, an inhibitor of angiogenesis, twice a week, for 3 weeks. The mice were sacrificed and immunohistochemical staining was employed to determine the microvessel density (MVD) and expression of integrin avβ3 in the lesion tissues. Results Lm609 inhibited the growth of the ectopic lesion. The lesion weighted 0.82±0.09 g in the treated group versus 0.51±0.93 g in the control group (P<0.05). The MVDs of the treated and control groups were 31.2±4.4 and 14.4±1.8 respectively (P<0.05). Conclusion Lm609 can inhibit the growth of ectopic lesion by reducing angiogenesis in SCID mouse.

中图分类号:

R711.71

赵军¹, 宗利丽², 李亚里¹. 整合素avβ3单克隆抗体对小鼠子宫内膜异位病灶的抑制作用[J]. 南方医科大学学报, 2005, 25(06): 709-711.

ZHAO Jun¹, ZONG Li-li², LI Ya-li¹. Inhibitory effects of integrin avβ3 monoclonal antibody on implanted lesions of endometriosis model of SCID mouse[J]. Journal of Southern Medical University, 2005, 25(06): 709-711.

参考文献

[1] Strathy JH, Molgaard CA, Coulam CB, et al. Endometriosis and infertility:a laparoscopic study of endometriosis among fertile and infertile women [J]. Fertil Steril, 1982, 38(6):667-72.
[2] Maas JWM, Le Noble FAC, Dunselman GAJ, et al. The chick embryo chorioallantoic membrane as a model to investigate the angiogenic properties of human endometrium [J]. Gynecol Obstet Invest, 1999, 48:108-12.
[3] Zamah NM, Dodson MG, Stephens LC, et al. Transplantation of normal and ectopic human endometrial tissue into athymic nude mice[J]. Am J Obstet Gynecol, 1984, 149:591-7.
[4] Blezinger P, Wang J. Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene[J]. Nat Biotechnol, 1999, 17(4):343-8.
[5] Breasalier RS, HO SB, Schoeppner HL, et al. Enhanced salvation of mucin-associated carbohydrate structures in human colon cancer metastasis [J]. Gastroenterology, 1996, 110(5):1354-67.
[6] Horton MA. The alpha v beta 3 integrin "vitronectin receptor" [J].Int J Biochem Cell Biol, 1997, 29721-5.
[7] Eliceiri BP, Cheresh DA. Role of alpha v integrins during angiogenesis[J]. Cancer J, 2000, 63:S245-9.
[8] Brooks PC, Stromblad S, Klemke R, et al. Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin[J]. J Clin Invest, 1995, 96:1815-22.
[9] Hii LL, Rogers PA. Endometrial vascular and glandular:expression of integrin alpha(v) beta3 in women with and without endometriosis[J]. Hum Reprod, 1998, 13(4):1030-5.
[10] Gutheil JC, Campbell TN, Pierce PR, et al. Targeted antiangiogenic therapy for cancer using Vitaxin:a humanized monoclonal antibody to the integrin alpha v beta3 [J]. Clin Cancer Res, 2000, 6 (8):3056-61.
[11] Sparano JA, Bernardo P, Stephenson P, et al. Randomized phase Ⅲtrial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy:Eastern Cooperative Oncology Group trial E2196[J]. J Clin Oncol, 2004, 22:4683-90.