重组血管内皮抑制素促BALB/c小鼠卵巢恶性肿瘤血管结构正常化的实验观察

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摘要目的探讨重组血管内皮抑制素注射液使人顺铂耐药性卵巢癌细胞裸小鼠原位移植模型肿瘤血管正常化的时间窗。方法 MTT(四甲基偶氮唑蓝还原反应)法确定SKOV3-DDP(人卵巢浆液性乳头状囊腺癌顺铂耐药株)细胞对顺铂的耐药性。利用SKOV3-DDP细胞系建立裸小鼠原位移植模型。30只裸鼠随机分为6组,每组5只,其中3组每次腹腔注射重组血管内皮抑制素(恩度)10 mg/kg,一次注射量均为0.2 ml,分别于第3、6、9天各处死一组;另3组分别作为对照组,每日腹腔内注射生理盐水0.2 ml,分别于第3、6、9天各处死一组。采用免疫荧光CD31染色检测恩度处理不同时间后肿瘤血管内皮细胞的完整性。结果生理盐水对照组的肿瘤血管结构紊乱迂曲、管径不一,且分支多,绝大多数外周被覆不完整的内皮细胞。而重组血管内皮抑制素给药3 d及9 d的血管完整性增加(23%±4.6%,17.7%±8.3%,P＞0.01),分支较少;特别是给药6 d后发现,血管管壁完整,直径均匀,完整性明显增加(75.3%±8.0%,P＜0.01,相比第3天及第9天)。结论重组血管内皮抑制素可使小鼠的卵巢癌血管正常化,这一现象为其与其他药物联合治疗提供了实验基础。

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	邱毓琪
	张雷
	易村犍
	刘香琼

关键词 ：重组血管内皮抑制素, 顺铂耐药性卵巢癌, 肿瘤血管正常化

Abstract：Objective To investigate the “time window” of Endostar (recombinant human endostatin) normalization of tumor vasculature in nude mouse model of orthotopic cisplatin (DDP)-resistant human ovarian cancer. Methods Methyl thiazolyl tetrazolium (MTT) assay was used to determine the DDP resistance of SKOV3-DDP (DDP-resistant human ovarian serous cystadenocarcinoma) cells, which were then used to establish orthotopic tumor model in nude mice. A total of 30 mice were randomly divided into 6 groups with 5 mice in each group. Among them, 3 groups were injected daily with 0.2 mL Endostar (10 mg/kg) intraperitoneally (i.p.) and sacrificed respectively 3, 6, and 9 days after the injection; the other 3 control groups were i.p. injected daily with 0.2 mL saline and sacrificed respectively 3, 6, and 9 days after the injection. The integrity of tumor vascular endothelial cells at different time points after Endostar treatment was measured by immunofluorescent staining of CD31. Results The tumor vasculatures in saline control groups were irregular and tortuous, with varied diameter and multiple branches, the vast majority of which were covered with incomplete endothelial cells. However, 3 and 9 days of Endostar administration improved the vascular integrity (23±4.6% and 17.7±8.3%, P>0.05) and reduced the number of vascular branches. In particular, the tumor vasculatures in mice treated with Endostar for 6 days showed complete vascular wall, uniform diameter, and significantly improved integrity (75.3±8.0%, P<0.01 vs. 3 and 9 days respectively). Conclusion Endostar treatment produced a short “time window” of normalization in tumor vasculature, which may provide an experimental basis for combination therapy

Key words： Endostar Cisplatin-resistant ovarian cancer Tumor vascular normalization

收稿日期: 2015-05-05

基金资助:湖北省医学领军人才培养工程专项经费项目[鄂卫生计生发(2013)4号] ;中华国际医学交流基金肿瘤专项基金资助 (CIMF-F-H001-267)

通讯作者: 刘香琼(lxq680401@163.com);易村犍(cunjiany@163.com)

引用本文:

邱毓琪, 张雷, 易村犍, 刘香琼. 重组血管内皮抑制素促BALB/c小鼠卵巢恶性肿瘤血管结构正常化的实验观察[J]. 中国生育健康杂志, 2015, 26(6): 525-528.
QIUYuqi, ZHANG Lei, YI Cunjian, LIU Xiangqiong. Endostar-induced temporary normalization of tumor vasculature in BALB/c model of SKOV3-DDP cell line. Chinese Journal of Reproductive Health, 2015, 26(6): 525-528.

链接本文:

http://cjrh.bjmu.edu.cn/CN/ 或 http://cjrh.bjmu.edu.cn/CN/Y2015/V26/I6/525

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