曾长青, 黄良祥, 黄海啸, 陈林昊, 郑羽, 池良杰. Fbxw7通过降解c-Myc和Cyclin E诱导胃癌细胞凋亡和生长阻滞[J]. 中国肿瘤临床, 2014, 41(3): 153-157. DOI: 10.3969/j.issn.1000-8179.20131891
引用本文: 曾长青, 黄良祥, 黄海啸, 陈林昊, 郑羽, 池良杰. Fbxw7通过降解c-Myc和Cyclin E诱导胃癌细胞凋亡和生长阻滞[J]. 中国肿瘤临床, 2014, 41(3): 153-157. DOI: 10.3969/j.issn.1000-8179.20131891
shu
ZENG Changqing, HUANG Liangxiang, HUANG Haixiao, CHEN Linhao, ZHENG Yu, CHI Liangjie. Fbxw7 induced cell apoptosis and growth retardation through degradation of c-Myc and Cyclin E in gastric cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2014, 41(3): 153-157. DOI: 10.3969/j.issn.1000-8179.20131891
Citation: ZENG Changqing, HUANG Liangxiang, HUANG Haixiao, CHEN Linhao, ZHENG Yu, CHI Liangjie. Fbxw7 induced cell apoptosis and growth retardation through degradation of c-Myc and Cyclin E in gastric cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2014, 41(3): 153-157. DOI: 10.3969/j.issn.1000-8179.20131891
shu

Fbxw7通过降解c-Myc和Cyclin E诱导胃癌细胞凋亡和生长阻滞

Fbxw7 induced cell apoptosis and growth retardation through degradation of c-Myc and Cyclin E in gastric cancer

    摘要
  • 摘要:
      目的  检测Fbxw7在胃癌组织中的表达并探讨其对胃癌细胞增殖和凋亡的影响。
      方法  免疫组织化学染色技术检测Fbxw7在20例胃癌及对应癌旁组织中的表达; 应用Fbxw7过表达质粒和Fbxw7 shRNA分别转染人胃癌细胞系MGC-803和AZ521, Western blot技术检测Fbxw7及其靶蛋白c-Myc和Cyclin E表达变化, 通过MTT和流式细胞术检测Fbxw7对胃癌细胞增殖和凋亡的影响。
      结果  Fbxw7在胃癌组织中的表达显著低于对应的癌旁组织(P < 0.05);Fbxw7过表达的MGC-803细胞中c-Myc和Cyclin E蛋白表达明显减少, Fbxw7过表达诱导细胞凋亡和生长阻滞(P < 0.05);敲低AZ521细胞中Fbxw7表达引起c-Myc和Cy- clin E蛋白蓄积, 导致细胞凋亡减少和增殖能力增强(P < 0.05)。
      结论  Fbxw7在胃癌组织中低表达, 其可能通过泛素化降解c-Myc和Cyclin E诱导胃癌细胞凋亡和生长阻滞, 提示Fbxw7在胃癌中可能作为关键抑癌因子发挥功能。

     

    Abstract:
      Objective  This study aimed to investigate the expression of Fbxw7 in gastric cancer tissues, and identify its effects on the proliferation and apoptosis of gastric cancer cells.
      Methods  Fbxw7 expression was detected in 20 samples of surgically resected paired gastric cancer and normal para-neoplastic tissues using immunohistochemistry.Fbxw7 and Fbxw7 shRNA plasmids were transfected into MGC-803 and AZ521 cells, respectively.The expression of c-Myc and Cyclin E, cell proliferation, and apoptosis were analyzed using western blot assay, MTT assay, and flow cytometry, respectively.
      Results  Fbxw7 expression was significantly lower in the gastric cancer tissues than that in the normal para-neoplastic tissues (P < 0.05).The ectopic expression of Fbxw7 downregulated the expression of c-Myc and Cyclin E, which resulted in the apoptosis and growth retardation of MGC-803 cells, respectively (P < 0.05). Fbxw7 knockdown led to c-Myc and Cyclin E protein accumulation, enhanced cell proliferation, and decreased apoptosis in AZ521 cells (P < 0.05).
      Conclusion  Fbxw7 expression was downregulated in gastric cancer, which possibly induced apoptosis and growth arrest through degradation of c-Myc and Cyclin E in gastric cancer cells.Thus, the loss of Fbxw7 may have an important function in the tumorigenesis of gastric cancer.

     

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