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靶向转录因子STAT3的Decoy核苷酸对膀胱癌细胞体外增殖的抑制作用
  • ISSN号:1007-385X
  • 期刊名称:《中国肿瘤生物治疗杂志》
  • 时间:0
  • 分类:R73-362[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]山东省医学科学院基础医学研究所,济南250062, [2]山东大学药学院免疫药理与免疫治疗研究所,济南250012
  • 相关基金:国家重点基础研究发展规划(973)资助项目(2004CB518807)和国家自然科学基金项目(30571696)
中文摘要:

目的:研究核转录因子STAT3的诱骗寡核苷酸(decoy ODNs)对人膀胱癌细胞系增殖的抑制作用,并探讨其作用机制。方法:采用阳离子聚合物Sofast为转染试剂将STAT3decoyODNs转染入膀胱癌T24及5637细胞;用MTY法检测细胞增殖情况;流式细胞术检测ODNs的转染效率;荧光显微镜检测ODNs人核情况;RT-PCR及Western blot检测转染ODNs前后bcl-xl、cyclinD1和c-myc表达水平的变化。结果:ODNs可有效地转染至细胞内,部分可进入核内,转染效率呈剂量依赖关系;STAT3 decoy ODNs可抑制膀胱癌细胞的增殖,100nmoL/L组抑制率最明显,达40%-48%;100nmoL/L decoy ODNs明显抑制bcl-xl、cyclinD1和c—myc mRNA及蛋白的表达水平。结论:STAT3 decoy ODNs可显著抑制膀胱癌细胞的增殖,其作用机制可能是通过下调癌基因c-myc、细胞周期基因cyclinD1及凋亡相关基因bcl-xl的基因转录及蛋白表达而实现的。

英文摘要:

Objective: To investigate the inhibitory effects of STAT3 decoy ODNs on the growth of human bladder cancer cell lines in vitro. Methods: STAT3 decoy and scramble ODNs were transfected into the bladder cell lines (T24 cells and 5637 cells) with Sofast, a positive compound transfection agent. MTT assay was used to detect cell growth rate; the transfection efficiency was detected by flow cytometry assay ;the locations of FITC labeled decoy ODNs were observed by reflected light fluorescence microscope ; and the expression of STAT3 downstream genes, such as bcl-xl, cyclinD1 and dc-myc mRNA and proteins, were examined by RT-PCR and Western bloting. Results: STAT3 decoy ODNs were effectively incorporated into the bladder cancer cells in a dose-dependent manner, and they inhibited the proliferation of cancer cells. The most obvious inhibition rate (40 % to 48% ) was found when the concentration of STAT3 decoy ODNs was at 100 nmol/L. The expression levels of Bcl-xl, c-myc and CylinD1 mRNA and protein were also significantly inhibited by 100 nmol/L STAT3 decoy ODNs. Conclusion: STAT3 decoy ODNs can obviously inhibit the proliferation of the bladder cancer cell lines T24 and 5637 , which may be associated with the inhibition of STAT3-mediated gene expression, such as bcl-xl,c-myc, and cylinD1.

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期刊信息
  • 《中国肿瘤生物治疗杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中国免疫学会 中国抗癌协会
  • 主编:曹雪涛
  • 地址:上海市杨浦区翔殷路800号
  • 邮编:200433
  • 邮箱:cjcb@biother.com
  • 电话:021-55620605-22 81871002-22
  • 国际标准刊号:ISSN:1007-385X
  • 国内统一刊号:ISSN:31-1725/R
  • 邮发代号:4-576
  • 获奖情况:
  • 《中国学术期刊(光盘版)检索与评价数据规范》第...
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  • 被引量:6458