沙利度胺和血管抑素在人宫颈癌小鼠异种移植模型中抑制肿瘤生长。

Thalidomide and angiostatin inhibit tumor growth in a murine xenograft model of human cervical cancer.

作者信息

Downs Levi S, Rogers Lisa M, Yokoyama Yumi, Ramakrishnan Sundaram

机构信息

The University of Minnesota Medical School, Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, 420 Delaware Street SE, MMC 395, Minneapolis, MN 55455, USA.

出版信息

Gynecol Oncol. 2005 Aug;98(2):203-10. doi: 10.1016/j.ygyno.2005.04.023.

DOI:10.1016/j.ygyno.2005.04.023

PMID:15975645

Abstract

OBJECTIVE

To determine the impact of thalidomide and angiostatin on tumor growth, angiogenesis, and apoptosis in a xenograft model of cervical cancer.

METHODS

Human umbilical endothelial cells were treated with angiostatin or thalidomide and bFGF-induced proliferation was assessed with the MTT assay. Human cervical cancer cells (CaSki and SiHa) were injected into the flanks of nude mice. After tumors developed, mice were treated with angiostatin 20 mg/kg/day or thalidomide 200 mg/kg/day for 30 days. Fractional tumor growth was determined and immunohistochemical analysis of tumors was used to determine degree of angiogenesis. TUNEL assay was used to assess apoptosis.

RESULTS

Angiostatin inhibited endothelial cell proliferation by 50-60%. Thalidomide had no direct effect on endothelial cells. Angiostatin and thalidomide both inhibited tumor growth by about 55%. We found no additive or synergistic effect when the two agents were combined. Both agents inhibited angiogenesis and induced apoptosis when compared to tumors from control animals.

CONCLUSIONS

Angiostatin and thalidomide inhibit tumor growth, angiogenesis, and induce apoptosis in this xenograft model of cervical cancer.

摘要

目的

在宫颈癌异种移植模型中确定沙利度胺和血管抑素对肿瘤生长、血管生成及细胞凋亡的影响。

方法

用人血管抑素或沙利度胺处理人脐静脉内皮细胞，采用MTT法评估碱性成纤维细胞生长因子诱导的增殖情况。将人宫颈癌细胞（CaSki和SiHa）接种于裸鼠侧腹。待肿瘤形成后，用血管抑素20mg/kg/天或沙利度胺200mg/kg/天处理小鼠，持续30天。测定肿瘤生长分数，采用肿瘤免疫组化分析确定血管生成程度。采用TUNEL法评估细胞凋亡情况。