靶向抑制Survivin途径对人卵巢癌细胞侵袭能力及其腹腔移植瘤生长的影响  

Effect of targeted inhibition of Survivin pathway on invasive ability of human ovarian cancer cells and growth of intraperitoneal xenografts

作　　者：孙艳[1] 底建敏[1] 陈春宁[2] 

机构地区：[1]河北医科大学第三医院妇产科 [2]河北医科大学第二医院妇产科,河北石家庄050000

出　　处：《中国妇幼保健》2015年第32期5654-5657,共4页Maternal and Child Health Care of China

基　　金：河北省自然科学基金资助项目〔H2013206198〕

摘　　要：目的通过分析靶向抑制Survivin基因表达后人卵巢癌SKOV3细胞系侵袭能力及其裸鼠腹腔移植瘤生长的变化,探讨靶向Survivin途径可能在抑制人卵巢癌SKOV3细胞系转移能力和腹腔移植瘤形成中的作用及可能的临床价值。方法用脂质体(Lipofectamine TM 2000)介导Survivin反义寡核苷酸(Survivin ASODN)转染人卵巢癌SKOV3细胞系,作为实验组(ASODN组),同时设空白脂质体作为对照组,通过Transwell小室检测两组细胞侵袭能力的改变。构建人卵巢癌SKOV3细胞系裸鼠腹腔转移瘤模型,通过Survivin ASODN腹腔注射干预,作为实验组(ASODN组),同时设生理盐水作为对照组,比较两组动物模型腹腔转移瘤生长情况的改变,并通过实时荧光定量PCR技术和蛋白印迹法检测人卵巢癌SKOV3细胞系和腹腔转移瘤组织中Survivin mRNA及蛋白表达的改变。结果转染Survivin ASODN后,人卵巢癌SKOV3细胞系侵袭能力均较对照组明显下降,差异有统计学意义(t=12.44,P<0.01)。经Survivin ASODN腹腔注射干预后,裸鼠腹腔移植瘤数量和重量都较对照组明显减小,差异均有统计学意义(t=12.36,P<0.01;t=3.00,P<0.01)。ASOND组人卵巢癌SKOV3细胞系及腹腔转移瘤组织中Survivin mRNA表达均较对照组明显下调,差异均有统计学意义(t=12.47,P<0.01;t=3.06,P<0.05);ASOND组人卵巢癌SKOV3细胞系及腹腔转移瘤组织中Survivin蛋白表达均较对照组明显下调,差异均有统计学意义(t=8.71,P<0.01;t=2.32,P<0.05)。结论靶向抑制Survivin途径不仅在活体外还在活体内均能有效降低卵巢癌细胞侵袭和转移能力,能有效抑制卵巢癌细胞腹腔转移瘤的形成和生长。腹腔注射Survivin ASODN可能成为临床防治卵巢癌复发和转移的重要生物治疗手段。Objective To explore the role and probable clinical value of Survivin pathway in inhibiting metastasis of human ovarian cancer SKOV3 cell line and formation of intraperitoneal xenografts by analyzing the invasive ability of human ovarian cancer SKOV3 cell line and change of growth of intraperitoneal xenografts among nude mice after targeted inhibition of Survivin pathway. Methods Liposome （ Lipo- fectamine TM 2000 ） -mediated Survivin antisense digonucleotides （Survivin ASODN ） was used to transfect human ovarian cancer SKOV3 cell line （experimental group, ASODN group ） ; blank liposomc was constructed as control group; Transwell assay was used to detect the changes of invasive ability of human ovarian cancer SKOV3 cell line in the two groups. Intraperitoneal xenografts nude mouse model of human ovarian cancer SKOV3 cell line was constructed, the mice in experimental group were treated with transabdominal injection of Survivin ASODN, while the mice in control group were treated with transabdominal injection of normal saline ; the changes of growth of intraperitoneal xenografts in the two groups were compared, fluorescence quantitative RT-PCR and Western blot were used to detect the changes of Survivin mRNA and protein in human ovarian cancer SKOV3 cell line and intraperitoneal xenografls. Results The invasive ability after transfection in experimental group was statistically significantly lower than that in control group （t= 12. 44, P〈0. 01 ） . The number and weight of intrap- eritoneal xenografts after transfection in experimental group were statistically significantly lower than those in control group （ t = 12. 36, P〈 0. 01 ; t=3.00, P〈0. 01 ） . The expressions of Survivin mRNA in human ovarian cancer SKOV3 cell line and intraperitoneal xenografts in experimental group were statistically significantly lower than those in control group （t= 12. 47, P〈0. 01 ; t=3.06, P〈0. 05） . The expres- sions of Survivin protein in human ovarian cancer SKOV3 cell line and intraperitoneal xenogr

关 键 词：卵巢癌 腹腔转移 反义寡核苷酸 SURVIVIN mRNA SURVIVIN蛋白 

分 类 号：R737.31[医药卫生—肿瘤]