沉默IL-17基因对裸鼠人上皮性卵巢癌移植瘤生长的抑制作用  

Inhibitory Effect of Silencing IL-17 Gene on Growth of Xenografts of Human Epithelial Ovarian Cancer in Nude Mice

作　　者：吴美琴 徐元萍 王勇[3] 宋晓婕[1] 李玉霞 刘智慧 王燕萍[4] 廖红玉[4] Wu Meiqin;Xu Yuanping;Wang Yong(Department of Gynecology and Obstetrics,Wuhan Children’s Hospital(Wuhan Maternaland Child Health Care Hospital),Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430015,China;Department of Gynecology and Obstetrics,The Third Hospital of Wuhan City(Tongren Hospital of Wuhan University),Wuhan 430074,China;Animal Laboratory Center of Wuhan University,Wuhan 430072,China)

机构地区：[1]华中科技大学同济医学院附属武汉儿童医院(武汉市妇幼保健院)妇科,武汉430015 [2]武汉市第三医院(武汉大学附属同仁医院)妇产科,武汉430074 [3]武汉大学动物实验中心,武汉430072 [4]湖北省中医院妇产科,湖北省中医药研究院,武汉430074

出　　处：《华中科技大学学报（医学版）》2020年第1期29-33,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：武汉市卫生计生委临床医学科研基金资助项目(No.WX17D16);湖北省科技厅科技条件资源开发项目[湖北省急危重症医学动物模型共享实验平台](No.2015BCE099)。

摘　　要：目的探讨IL-17基因对裸鼠人上皮性卵巢癌移植瘤生长的影响,为寻找治疗卵巢癌可能的新靶标奠定基础。方法选取对数生长期的人上皮性卵巢癌细胞株SKOV3建立裸鼠人上皮性卵巢癌移植瘤模型,将造模成功的裸鼠随机分成对照组和IL-17-siRNA组。3周后颈椎脱臼法处死裸鼠,分离肿瘤组织,测量肿瘤的体积。取每组均数制作肿瘤生长曲线,以TUNEL法检测肿瘤细胞的凋亡,以ELISA法检测血清中IL-17、IL-4、IFN-γ和TNF-α的水平;以Western blot法检测p-JAK、JAK、p-STAT3、STAT3、Caspase-3、Caspase-8、Caspase-9的表达水平,以免疫组化法检测血管内皮生长因子A(vascular endothelial growth factor A,VEGF-A)和CD34的表达水平。结果和对照组比较,IL-17-siRNA组的肿瘤体积逐渐增加,在第21天时,IL-17-siRNA组的肿瘤体积显著小于对照组,IL-17-siRNA组的细胞凋亡率显著升高,IL-17-siRNA组的p-JAK和p-STAT3表达显著降低,Caspase-3、Caspase-8、Caspase-9的表达显著升高(均P<0.05)。结论敲降IL-17基因可能通过抑制IL-17-STAT3信号通路,抑制VEGF-A的表达,抑制卵巢肿瘤细胞的迁移,促进肿瘤组织细胞凋亡,减缓卵巢癌的发展。Objective To investigate the effect of IL-17 on the growth of human epithelial ovarian cancer xenografts in nude mice,and to lay a foundation for finding new targets for the treatment of ovarian cancer.Methods The human epithelial ovarian cancer cell line SKOV3 in logarithmic growth phase was selected to establish a human epithelial ovarian cancer xenograft model in nude mice.Nude mice were randomly divided into control group and IL-17-siRNA group.After 3 weeks,the nude mice were sacrificed by cervical dislocations,and then the tumor tissues were separated and the volume of the tumor was measured.The expression of p-JAK,JAK,p-STAT3,STAT3,Caspase-3,Caspase-8 and Caspase-9 was detected by Western blotting.Vascular endothelial growth factor A(VEGF-A) and CD34 was detected by immunohistochemistry.Results Compared with the control group,the tumor volume of IL-17-siRNA group increased gradually.On the 21 st day,the tumor volume of IL-17-siRNA group was significantly smaller than that of the control group,the apoptosis rate of IL-17-siRNA group was significantly increased,the expression of p-JAK and p-STAT3 in IL-17-siRNA group was significantly decreased,and the expression of Caspase-3,Caspase-8,Caspase-9 was significantly increased(all P<0.05).Conclusion Knocking down IL-17 gene may inhibit the expression of VEGF-A,migration of ovarian tumor cells,promote apoptosis of tumor cells and slow down the development of ovarian cancer through inhibiting IL-17-STAT3 signaling pathway.

关 键 词：血管内皮生长因子A 凋亡 迁移 卵巢癌 

分 类 号：R737.3[医药卫生—肿瘤]