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山东大学学报(医学版) ›› 2014, Vol. 52 ›› Issue (1): 20-22.doi: 10.6040/j.issn.1671-7554.0.2013.032

• 基础医学 • 上一篇    下一篇

TIPE2在结肠癌发展中的作用及分子机制

李雪梅1, 颜世平1, 宿敬然2,程兆令1, 朱强1   

  1. 1.山东大学附属省立医院消化内科,济南 250021;2.山东大学医学院,济南 250012
  • 收稿日期:2013-01-10 出版日期:2014-01-10 发布日期:2014-01-10
  • 通讯作者: 朱强,E-mail:zhuqiang@medmail.com.cn
  • 基金资助:

    山东省中青年科学家科研奖励基金(BS2009YY022)。

Role and molecular mechanism of TIPE2 in the progression of colon cancer

LI Xue-mei1, YAN Shi-ping1, SU Jing-ran2, CHENG Zhao-ling1, ZHU Qiang1   

  1. 1. Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China;
    2. School of Medicine, Shandong University, Jinan 250012, China
  • Received:2013-01-10 Online:2014-01-10 Published:2014-01-10

摘要:

目的  探讨肿瘤坏死因子α诱导蛋白8样因子2(TIPE2)是否通过结合caspase-8抑制toll 样受体4(TLR4)通路参与结肠癌发展。 方法Si-RNA转染降低HT-29中TIPE2表达,采用实时定量PCR验证。用浓度为1μg/mL脂多糖(LPS)激活TLR4通路,在TIPE2降低组、TLR4激活组、TIPE2降低且TLR4激活组及野生型细胞组中检测caspase-8活性。 结果实时定量PCR检测到TIPE2-siRNA成功降低了TIPE2的表达。在TIPE2降低组和TLR4 激活组中caspase-8活性高于野生型细胞组(P<0.05), TIPE2降低且TLR4激活组高于TLR4 激活组(P<0.05)。 结论TIPE2可以抑制结肠癌细胞中caspase-8活性,并通过结合caspase-8抑制TLR4通路参与结肠癌发展。

关键词: 肿瘤坏死因子&alpha, 诱导蛋白8样因子;Toll 样受体4;Caspase-8;结肠癌;结肠炎症

Abstract:

Objective  To explore whether tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) inhibits toll-like receptor 4 (TLR4) pathway by binding to caspase-8 to participate in the progression of colon cancer. Methods  TIPE2 expression was down-regulated in HT-29 cells by small RNA interference technology. TLR4 pathway was activated with 1μg/mL lipopolysaccharide (LPS). Caspase-8 activities were detected in the TIPE2 knockdown cells, TIPE2 knockdown & TLR4 activation cells, TLR4 activation cells and wild-type cells. Results  Real-time PCR found that TIPE2-siRNA decreased the TIPE2 expression successfully. Caspase-8 activities were higher in TIPE2 knockdown cells and TLR4 activation cells than in wild-type cells (P<0.05). Caspase-8 activities were higher in TIPE2 knockdown & TLR4 activation cells than in TLR4 activation cells (P<0.05). Conclusion  TIPE2 can inhibit caspase-8 activity and it is involved in the progression of colon cancer through its binding to caspase-8 which negatively regulates TLR4 pathway.

Key words: Toll-like receptor 4, Colon tumorogenesis, Colon inflammation, Tumor necrosis factor- α-induced protein-8, Caspase-8

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[2] 亓珅,韩晓娟,王璐,张清华,杜怡峰. 海风藤提取物对激活的小胶质细胞IL-1β和TNF-α表达的影响[J]. 山东大学学报(医学版), 2013, 51(5): 11-14.
[3] 耿超1,潘英芳2,林森1. 肿瘤坏死因子α诱导蛋白8对胃癌细胞转移能力的影响[J]. 山东大学学报(医学版), 2013, 51(5): 85-88.
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