期刊文献+

Survivin反义寡核苷酸对人卵巢癌细胞裸鼠腹腔移植瘤生长的影响与机制 被引量:5

Effects of anti- survivin oligonucleotides on growth of peritoneally implanted ovarian cancer xenografts in nude mice
下载PDF
导出
摘要 目的探讨survivin反义寡核苷酸(ASODN)在活体内对人卵巢癌细胞种植性转移能力和腹腔移植瘤形成的影响,分析其可能的作用机制。方法构建人卵巢癌SKOV3细胞株裸鼠腹腔移植瘤模型,实验组给予survivin ASODN腹腔注射,同时对照组给予生理盐水腹腔注射,比较两组动物腹腔移植瘤形成和生长情况的改变,并通过蛋白印迹法检测两组腹腔移植瘤组织中白细胞介素6(IL-6)、信号转导与活化因子3(STAT3)、磷酸化的信号转导与活化因子3(p-STAT3)、survivin蛋白表达的改变。结果Survivin ASODN组人卵巢癌细胞裸鼠腹腔移植瘤数量和重量都较对照组明显减小(P<0.05),IL-6、STAT3、p-STAT3、survivin蛋白表达均明显下降(P<0.05)。结论 Survivin ASODN在活体内能有效降低人卵巢癌细胞侵袭和种植性转移能力,能有效抑制卵巢癌腹腔移植瘤的生长,这些作用是通过抑制IL-6/STAT3信号通路的活性来完成的。靶向survivin基因的反义核苷酸治疗将成为临床防治卵巢癌复发和转移重要手段,有重要的临床价值。 Objective To observe the effect of anti-survivin oligonucleotides (ASODN) on the invasion and growth of peritoneally implanted ovarian cancer cell xenografts in nude mice. Methods Nude mouse models bearing peritoneally implanted ovarian cancer cell (SKOV3) xenografts were established and subjected to intraperitoneal injection of survivin ASODN or saline (control). The number and weight of the intraperitoneal xenografts were compared between the two groups. The expressions of interieukin (IL-6), signal transducer and activator of transcription3 (STAT3), phosphorylated STAT3 (p-STAT3), and survivin protein in the tumor tissues were detected with Western blotting in both groups. Results Compared with those in the control group, the number and weight of the intraperitoneal xenografts were significantly reduced in ASODN group (P〈0.05). ASODN treatment also resulted in significantly lowered protein levels of IL-6, STAT3, p-STAT3, and survivin in the tumor tissues (P〈0.05). Conclusion Survivin ASODN can suppress the invasion and migration capacity of ovarian cancer cells and inhibit peritoneal metastasis of the tumor in nude mice possibly though down-regulation of IL-6/ STAT3 signaling pathway.
出处 《南方医科大学学报》 CAS CSCD 北大核心 2015年第8期1211-1214,F0003,共5页 Journal of Southern Medical University
基金 河北省自然科学基金(H2013206198)
关键词 卵巢癌 腹腔转移 survivin 反义寡核苷酸 IL-6/STAT3信号通路 ovarian cancer peritoneal metastasis survivin oligonucleotides IL-6/STAT3 signaling pathway
  • 相关文献

参考文献17

  • 1Chen L,Liang L,Yan X,et al.Survivin status affects prognosis and chemosensitivity in epithelial ovarian cancer [J],Int J Gynecol Cancer,2013,23(2):256-63.
  • 2Kumar J,Fraser FW,Riley C,et al.Granulocyte colony-stimulating factor receptor signalling via Janus kinase 2/signal transducer and activator of transcription 3 in ovarian cancer[J].Br J Cancer,2014,110(1):133-45.
  • 3Paul BT,Blanchard Z,Ridgway M,et al.BRCAI-IRIS inactivation sensitizes ovarian tumors to cisplatin[J].Oncogene,2015,34(23):3036-52.
  • 4Suh YA,Jo SY, Lee HY,et al.Inhibition of IL-6/STAT3 axis and targeting Axl and Tyro 3 receptor tyrosine kinases by apigenin circumvent taxol resistance in ovarian cancer cells [J].Int J Oncol,2015,46(3):1405-11.
  • 5Kumar J,Ward AC.Role of the interleukin 6 receptor family in epithelial ovarian cancer and its clinical implications [J].Biochim Biophys Acta,2014,1845(2):117-25.
  • 6No JH,Jeon YT,Kim YB,et al.Quantitative detection of serum survivin and its relationship with prognostic factors in ovarian cancer[J].Gynecol Obstet Invest,2011,71(2):136-40.
  • 7Kusku Cabuk F,Yigit S,Demir L,et al.Correlation of survivin and MMP9 expressions with prognosis and clinicopathological parameters in surface epithelial ovarian carcinomas [J].Turk Patoloji Derg,2014,30(1):30-7.
  • 8Rodel F,Sprenger T,Kaina B,et al.Survivin as a prognostic/ predictive marker and molecular target in cancer therapy [J].Curr Med Chem,2012,19(22);3679-88.
  • 9孙艳,李勇,范立侨,吴小华,程建新,赵群.Survivin反义寡核苷酸对卵巢癌细胞株凋亡和侵袭、迁移的影响[J].肿瘤,2007,27(9):694-697. 被引量:3
  • 10Carrasco RA,Stamm NB,Marcusson E,et al.Antisense inhibition of survivin expression as a cancer therapeutic [J].Mol Cancer Ther,2011,10(2):221-32.

二级参考文献13

  • 1张惠忠,魏益平,华平,李海刚,刘金耿,吴澄,曹永科.非小细胞肺癌血管内皮生长因子-C和Survivin蛋白的表达及其对患者预后的影响[J].中山大学学报(医学科学版),2006,27(6):681-685. 被引量:7
  • 2OLIE R A,SIM ES-WuST P A,BAUMANU B,et al.A novel antiSense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy[J].Cancer Res,2000,60(11):2805-2809.
  • 3LI A,DUBEY S,VARNEY M L,et al.IL-8 directly enhanced endothelial cell survival,proliferation,and matrix metalloproteinases production and regulated angiogenesis[J].J Immunol,2003,170(6):3369-3376.
  • 4DEVERAUX Q L,REED J C.1AP family proteins-suppressors of apoptoais[J].Genes Dev,1999,13(3):239-252.
  • 5ZAMAN G J R,CONWAY E M.The elusive factor X a receptor:failure to detect transcripts that correspond to the published seqoence of EPR-1[J].Hemostasis Blood,2000,96(1):145-148.
  • 6SKOUFIAS DA,MOLLINARI C,LACROIX F B,et al.Human surviving is a kinetoehore-associated passenger protein[J].J Cell Biol,2000,15(7):1575-1582.
  • 7KASHKAR H,HAEFS C.XIAP-mediated caspase inhibition in Hodgkins iymphoma-derived B cells[J].J Exp Med,2003,198(2):341-347.
  • 8CREAGH EM,MURPHY B M,DURIEZ PJ,et al.Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor apoptosis proteins[J].J Biol Chem,2004,279(26):26906-26914.
  • 9YANG Q H,DU C.Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in Hela cells[J].J Biol Chem,2004,279(17):16963-16970.
  • 10DIAS S,HATFORI K,HEISSIG B,et al.Inhibition of both paracrine and autocrine VEGF/VEGFR-signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias[J].Proc Natl Acad Sci USA,2001,98(19):10857-10862.

共引文献2

同被引文献135

  • 1许斌,肖蔚,焦霞,赵燕,蒋小芹,于鸿.生存素反义寡核苷酸对乳腺癌MCF-7细胞株MMP-2及MMP-9表达的影响[J].江苏大学学报(医学版),2011,21(3):203-207. 被引量:5
  • 2Qian-Rong Qi,Zeng-Ming Yang.Regulation and function of signal transducer and activator of transcription 3[J].World Journal of Biological Chemistry,2014,5(2):231-239. 被引量:23
  • 3HongZhu Xiao-PingChen Wan-GuangZhang Shun-FengLuo Bi-XiangZhang.Expression and significance of new inhibitor of apoptosis protein survivin in hepatocellular carcinoma[J].World Journal of Gastroenterology,2005,11(25):3855-3859. 被引量:31
  • 4Wang B, Liu SZ, Zheng RS, et al. Time trends of ovarian cancer incidence in China[J]. Asian Pac J Cancer Prev, 2014, 15(1): 191-3.
  • 5Vergote I. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer[J]. N Engl J Med, 2010, 363(10): 943-53.
  • 6Mazda M, Nishi K, Naito Y, et al. E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing [J]. PLoS One, 2011, 6(12): e28688.
  • 7Vandewalle CV, Berx G. The role of the ZEB family of transcription factors in development and disease[J]. Cell Mol Life Sci, 2009, 66 (5): 773-87.
  • 8Kahlert C, Lahes S, Radhakrishnan P, et al. Overexpression of ZEB2 at the invasion front of eolorectal cancer is an Independent prognostic marker and regulates tumor invasion in vitro [J]. Clin Cancer Res, 2011, 17(24): 7654-63.
  • 9Okugawa Y, Inoue Y, Tanaka K, et al. Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer[J]. Clin Exp Metastasis, 2013, 30(4): 417-29.
  • 10Karihtala P, Auvinen P, Kauppila S, et al. Vimentin, zebl and sip1 are up-regulated in triple-negative and basal-like breast cancers: association with an aggressive tumour phenotype[J]. Breast Cancer Res Treat, 2013, 138(1): 81-90.

引证文献5

二级引证文献14

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部