微信公众号

官网二维码
中国癌症防治杂志

中国癌症防治杂志 ›› 2015, Vol. 7 ›› Issue (3): 182-187.doi: 10.3969/j.issn.1674-5671.2015.03.09

• 基础研究 • 上一篇    下一篇

应用基因表达谱芯片技术研究Rituximab的耐药机制

  

  1. 广西医科大学附属肿瘤医院化疗三科
  • 出版日期:2015-06-25 发布日期:2015-07-13
  • 通讯作者: 岑洪 cen_hong@163.com
  • 基金资助:

    国家自然科学基金资助项目（81160298）；广西医疗卫生重点科研课题（重2011077）；广西医疗卫生适宜技术研究与开发课题 （S201301-02）

Preliminary cDNA microarray studies of Rituximab resistance mechanisms

  • Online:2015-06-25 Published:2015-07-13

PDF (PC)

454

赞

被引次数

1

摘要：

目的 应用基因表达谱芯片技术检测Rituximab耐药细胞株差异表达基因、富集信号通路及相关生物学行为，初步探讨Rituximab的耐药机制。方法 成功构建Rituximab耐药B细胞性非霍奇金淋巴瘤细胞株Jeko-1/R和Raji/R，应用基因表达谱芯片技术检测耐药细胞株与亲本细胞株的差异表达基因，用KEGG数据库及DAVID软件进行生物信息学分析。结果 在两株Rituximab耐药细胞株中，同为上调和同为下调表达的差异基因分别有70个和42个；KEGG 通路分析提示Rituximab耐药细胞与亲本细胞相比，MAPK信号通路呈富集；基因本体论（gene ontology，GO）分析提示耐药细胞生物学行为表现主要集中在抗凋亡、促增殖、促血管发育等方面。结论 与Rituximab耐药关系最密切的通路可能为MAPK信号通路，其机制可能是Rituximab激活MAPK信号通路后抑制肿瘤细胞凋亡，促进肿瘤细胞增殖及促进肿瘤血管发育，这为预测Rituximab耐药及逆转耐药提供了理论依据。

关键词: 淋巴瘤, Rituximab, 药物耐药, 基因表达谱芯片, MAPK信号通路, 生物信息学

Abstract:

Objective In this study，we aimed to use cDNA microarrays to identify differentially expressed genes and activation or inhibition of signaling pathways that may account for the phenotype of rituximab-resistant cell lines. Methods Rituximab-resistant B-cell non-Hodgkin′s lymphoma cell lines were established，and cDNA microarray analysis was performed on the resistant and parental cell lines. Bioinformatics analysis was carried out using the KEGG database and DAVID software. Results We identified 70 genes that were up-regulated and 42 that were down-regulated in both Jeko-1/R and Raji/R resistant cell lines compared to parental lines. KEGG pathway analysis suggested that the MAPK signaling pathway is significantly more active in Jeko-1/R and Raji/R cells. GO term analysis of differentially expressed genes suggested that rituximab-resistant cells show the characteristics of “anti-apoptosis”， “promoting proliferation” and “blood vessel development”. Conclusion Our results suggest that rituximab resistance is most closely associated with the MAPK signaling pathway， which may act to inhibit apoptosis and promote proliferation and vascular development. These findings provide a theoretical basis for predicting and overcoming rituximab resistance in the clinical setting.

Key words: Lymphoma, Rituximab, Drug resistance, cDNA microarray, MAPK signaling pathway, Bioinformatics