RhoA基因沉默抑制卵巢癌腹腔移植瘤恶性生物学行为的研究  

Inhibitory effects of RhoA gene silence on malignant biological behaviors of human ovarian cancer in nude mice intraperitoneal xenograft

作　　者：蒋文燕[1] 康佳丽[1] 王小霞[1] 杨文娟[1] 聂妙玲[1] 周聪[1] 

机构地区：[1]广州医学院附属广州市第一人民医院妇产科,广东广州510180

出　　处：《现代肿瘤医学》2013年第7期1468-1473,共6页Journal of Modern Oncology

基　　金：广东省科学计划项目(编号:2010B031600185)

摘　　要：目的:研究慢病毒介导RhoA基因沉默对人卵巢癌裸鼠腹腔移植瘤生长、侵袭及转移等恶性生物学行为的影响。方法:21只裸鼠随机分为HO8910-RhoA-shRNA组、HO8910-RhoA-NC组和HO8910组,每组7只。细胞接种法建立人卵巢癌腹腔移植瘤模型,每2天测量腹围。4周后解剖裸鼠,大体观察,测定腹水量,统计肿瘤播散器官数及瘤结节数。称量瘤体重量,并计算抑瘤率。镜下观察,应用HE染色分析移植瘤病理形态学特点。实时荧光定量PCR和Western blot检测移植瘤RhoA mRNA和蛋白表达情况。TUNEL技术检测移植瘤凋亡指数(apoptotic index,AI)。结果:与HO8910-RhoA-NC组和HO8910组比较,HO8910-RhoA-shRNA组裸鼠腹围增长明显滞后(P<0.05),腹水量明显减少(P=0.01),肿瘤播散器官数、瘤结节数及瘤体重量均明显减少(P均<0.001),抑瘤率达70.62%。RhoA基因mRNA和蛋白表达水平均显著下降(P均<0.001)。凋亡指数AI明显升高(P<0.001)。结论:慢病毒靶向沉默RhoA基因能显著抑制人卵巢癌裸鼠腹腔移植瘤的恶性生物学行为。Objective：To investigate the effects of RhoA gene silence on the malignant biological behaviors of ovarian xenograft in nude mice in vivo.Methods：Twenty one female nude mice were randomly assigned to three groups： HO8910-RhoA-shRNA group,HO8910-RhoA-NC group and HO8910 group.The stable knockdown of RhoA cell line,negative control cell line and ovarian cancer cell line HO8910 were inoculated respectively into abdominal cavity of each group to establish intraperitoneal xenograft model of human ovarian cancer.Abdominal circumference were recorded every two days,the nude mice were sacrificed four weeks after-inoculation.The ascitic volume,dissemination position number,disseminated tumor number,tumor weight and tumor growth inhibition rate were recorded.Histopathological analysis for xenograft tissues were observed by HE staining.The expression of RhoA mRNA and protein of xenograft tissues were detected by real-time qPCR and Western blot.Cell apoptosis in tumor tissues was observed by TUNEL method and apoptotic index（AI） were counted.Results：Abdominal circumference in HO8910-RhoA-shRNA group growth delay were statistically significant（P0.05）.The HO8910-RhoA-shRNA group had decreased in ascitic volume（P=0.01）,dissemination position number（P0.001）,disseminated tumor number（P0.001） and tumor weight（P0.001）,with tumor growth inhibition rate of 70.62%.The relative expression of RhoA mRNA and protein were both significantly decreased in HO8910-RhoA-shRNA group（P0.001）.AI was significantly increased in HO8910-RhoA-shRNA group（P0.001）.Conclusion：RhoA gene silenced by Lentivirus-mediated RNAi can significantly suppress the malignant biological behaviors of human ovarian cancer in nude mice xenograft.

关 键 词：RHOA 卵巢肿瘤 慢病毒 异种移植模型抗肿瘤试验 肿瘤浸润 凋亡 

分 类 号：R737.31[医药卫生—肿瘤]