重组人血管内皮抑制素注射液对宫颈癌裸鼠移植瘤生长转移及血管淋巴管生成的抑制作用

Endostar reduces the growth and metastasis by inhibiting angiogenesis and lymphangiogenesis in nude mouse models of human cervical cancer

目的观察重组人血管内皮抑制素注射液（商品名恩度^R）对宫颈癌裸鼠移植瘤生长、转移及血管、淋巴管生成的抑制作用。方法以人宫颈癌HeLa细胞株接种BALB／c—nu雌性裸鼠，建立动物模型。随机将裸鼠分为对照组、顺铂组、恩度组、小剂量恩度（10mg／kg）＋顺铂组和大剂量恩度（20mg／kg）＋顺铂组等5组，观察肿瘤生长和淋巴结转移情况。采用免疫组织化学法检测移植瘤的微血管密度（MVD）和微淋巴管密度（MLD）。结果大剂量恩度＋顺铂组、小剂量恩度＋顺铂组和恩度组的肿瘤生长速度明显慢于对照组和顺铂组（P〈0．05）。大剂量恩度＋顺铂组、小剂量恩度＋顺铂组、恩度组、顺铂组和对照组的裸鼠肿瘤淋巴结转移率分别为0（0／8）、12．5％（1／8）、12．5％（1／8）、62．5％（5／8）、75．0％（6／8，P=0．002）。大剂量恩度＋顺铂组、小剂量恩度＋顺铂组、恩度组、顺铂组和对照组的裸鼠肿瘤MVD分别为10．88±1．38、10．25±1．22、10．83±2．29、15．58±2．31和22．08±1．93（P=0．000），MLD分别为5．00±0．63、5．17±0．75、6．00±0．63、14．33±1．63和13．67±1．21（P=0．000）。结论恩度可以通过抑制裸鼠宫颈癌模型的血管和淋巴管生成，而抑制肿瘤的生长和淋巴结转移。

Objective To observe the influence of endostar alone or in combination with cisplatin on tumor growth and metastasis, as well as the inhibition of angiogenesis and lymphangiogenesis in nude mouse models of human cervical cancer. Methods HeLa cells were inoculated subcutaneously into the hind flank region of female nu/mice to establish xenograft models. The nude mice were randomly divided into 5 groups ： （ 1 ） sodium chloride （ as control ） ; （ 2 ） cisplatin alone ; （ 3 ） endostar alone ; （ 4 ） cisplatin plus endostar （10 mg/kg） ; （5） cisplatin plus endostar （20 mg/kg）. The course of all the treatments lasted for 4 weeks. The tumor growth and lymph node metastasis were observed. Immunohistochemical staining was employed to detect the angiogenesis and lymphangiogenesis. Results （1） Either eudostar alone or endostar with cisplatin inhibited the tumor growth significantly than cisplatin and NS （ P 〈 0.05 ）. （2） The rates of lymph node metastasis in the endostar（20 mg/kg）with cisplatin, the endostar（ 10 mg/kg）with cisplatin, the endostar, the cisplatin and the NS groups were 0 （ 0/8 ）, 12.5 % （ 1/8 ） , 12.5 % （ 1/8 ）, 62.5 % （ 5/8 ） and 75.0% （6/8） （ P = 0. 002 ）, respectively. （ 3 ） The MVD of tumor tissue in these five groups were 10.88 ＋ 1.38, 10.25 ± 1.22, 10.83± 2.29, 15.58 ± 2.31 and 22.08± 1.93, respectively（ P 〈 0.05 ）. The MLD were 5.00 ±0.63, 5.17 ＋0.75, 6.00±0.63, 14.33 ± 1.63 and 13.67 ± 1.21, respectively （P 〈 0.05）. Conclusion Endostar can reduce the tumor growth and metastasis by inhibiting angiogenesis and lymphangiogenesis in nude mouse model of human cervical cancer.