舒尼替尼及联合顺铂对小儿睾丸卵黄囊瘤荷瘤鼠模型的抗肿瘤作用  

Antitumor effects of Sunitinib or Sunitinib combind with cis-diamminedichloroplatinum on an athymicmouse human testicular yolk sac tumor xenograft model

作　　者：赵军锋[1] 林杰[1] 吕文强[1] 陈聪德[1] 秦乐[1] 张浩川[1] 陈肖鸣[1] 李仲荣[1] 

机构地区：[1]温州医学院育英儿童医院小儿外科,325027

出　　处：《中华小儿外科杂志》2011年第8期610-615,共6页Chinese Journal of Pediatric Surgery

基　　金：浙江省卫生厅重点项目（编号：2004ZD009）

摘　　要：目的探讨舒尼替尼（Sunitinib）、顺铂（CDDP）及两者联合用药对小儿睾丸卵黄囊瘤（TYST）异种移植荷瘤鼠模型的抗肿瘤作用及相关作用机制。方法肿瘤标本来自本实验室的小儿,睾丸卵黄囊瘤裸鼠第17代模型，并接种在雄性裸鼠单侧腹股沟皮下区，成瘤后随机分成4组（n=5）：对照组、CDDP组、Sunitinib组和Sunitinib＋CDDP组。绘制肿瘤体积和裸鼠体重变化曲线图，计算肿瘤消退率；HE染色观察肿瘤组织形态学变化；免疫组织化学法检测AFP、Ki-67、Glypican-3、CD105在各组肿瘤中的表达：CD105测定微血管密度（MVD），Ki-6表示细胞增殖率（PI）；TUNEL法检测肿瘤细胞凋亡率（AI）；实时荧光定量PCR（RT-qPCR）验证靶向因子的mRNA表达变化。结果各治疗组均能显著抑制肿瘤生长，并能消退肿瘤体积。在治疗后肿瘤体积上，除顺铂组与舒尼替尼组间无统计学差异外（41．61±7．61比67．15±5．39，P〉0．05），其余各组间都有统计学差异：对照组与顺铂（651．72±121．16比41．61±7．61，P＜0．05），对照组与舒尼替尼组（651．72±121．16比67．15±5．39，P〈0．05），对照组联合舒尼替尼±顺铂组（651．72±121．16比23．03±2．37，P〈0．05），舒尼替尼组与联合舒尼替尼＋顺铂组（67．15±5．39比23．03±2．37，P〈O．05），顺铂组与联合舒尼替尼＋顺铂组（41．61±7．61比23．03±2．37，P％0．05）；在裸鼠体重上，相比对照组，除舒尼替尼组无统计学差异外（25．90±0．75比26．66±0．65，P〉0．05），其余各组间差异均有统计学意义：对照组与顺铂组（25．90±0．75比18．90±0．63，P〈O．05），对照组与联合舒尼替尼＋顺铂组（25．90±0．75比18．26±1．20，P〈0．05）；AFP、Glypican-3在各治疗组阳性表达面积（Pixels）均少于对照组（AFP：对照组与顺铂组，1．26×10＾6±1．48×10＾5比5．54×10＾5±8�Objective To study the antitumor effects of Sunitinib or Sunitinib combind with cis - diamminedichloroplatinum （CDDP） on an athymic mouse human testicular yolk sac tumor xenograft model. Methods The athymic mouse human testicular yolk sac tumor xenograft model was established by subcutaneous injection of 17th passage pediatric testicular yolk sac tumor cells in the unilateral inguinal region of the male nude mice. The mice of control group didn＇t receive any treatment. The tumor bearing mice were treated with either CDDP, or Sunitinib group, or Sunitinib combined with CDDP. The tumor-bearing nude mice were divided into 4 groups （5 in each） according the treatment they underwent. The tumor volumes and mice weight were measured to calculate the regression rate of tumor. The tumor was collected for H＆E staining and immunohistochemical staining of AFP, Ki-67, Glypican-3 and CD105. Microvessel density （MVD） was measured by analyzing the CD105 expression. The tumors＇ proliferation index （PI） was studied by analyzing Ki-67 expression. The apoptosis of the tumor was quantitated using TUNEL staining. The mRNA expressions of cytokines were determined by quantitative real-time PCR （RT-qPCR）. Results The tumor volumes were significantly decreased after chemotherapy. No difference of tumor volume was found between CDDP group and Sunitinib group （41.61 ± 7. 61 vs. 67. 15 ±5.39, P〉0. 05）. Significant differences of tumor volumes were found between CDDP group and CDDP＋ Sunitinib group （41.61± 7. 61 vs. 23. 03 ± 2. 37, P〈0. 05）, and between Sunitinib group and CDDP＋ Sunitinib group （67. 15 ± 5.39 vs. 23.03 ±2. 37, P 〈0. 05）. Of the body weight of tumor-bearing mice, no difference was found between controls and Sunitinib group （25.90 ±0. 75 vs. 26. 66 ± 0. 65, P〉0. 05）. And significant differences of the body weight were noted between controls and CDDP group （25.90 ± 0. 75 vs. 18. 90±0. 63,P〈0. 05）, controls and CDDP＋ Sunitinib group （25.90 ±0. 75 vs. 18.

关 键 词：舒尼替尼 顺铂 卵黄囊瘤 睾丸 

分 类 号：R737[医药卫生—肿瘤] R-332[医药卫生—临床医学]