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目的利用小分子干扰RNA(siRNA)和基因芯片技术初步筛选人胰腺癌细胞信号转导及转入激活因子3(STAT3)下游耐药相关基因,为探索STAT3调控耐药机制提供依据。方法利用基因芯片技术比较人胰腺癌细胞SW1990与siRNA沉默STAT3后SW1990细胞中基因表达的差异,初步筛选STAT3下游耐药相关基因。结果按差异显著性标准从47 000条基因(代表38 500个明晰的基因)中筛选出具有表达差异的基因共有982条(2.55%),其中上调表达2倍的基因有592条,下调表达2倍的基因有390条。与耐药相关基因有:显著上调的拓扑异构酶IIα(TOPOIIα)、肿瘤坏死因子凋亡诱导相关配体(TRAIL);显著下调的富半胱氨酸61(CYR61),Ras肿瘤基因家族成员(RAP1A),bcl-2相关抗凋亡基因(BAG1),囊性纤维化跨膜转导调节因子(CFTR)。结论胰腺癌耐药是一个多基因、多通路相互作用的结果。应用siRNA技术沉默STAT3基因后,有6条耐药相关基因发生改变。为进一步研究STAT3与胰腺癌耐药的关系提供新的线索,也为胰腺癌的治疗提供新的思路。
OBJECTIVE: To screen primary human pancreatic cancer cell signal transduction transduction-related genes downstream of activator of transcription 3 (STAT3) by using small interfering RNA (siRNA) and gene chip technology, and to provide basis for exploring the mechanism of STAT3 regulation of drug resistance. Methods The gene expression profiles of human pancreatic cancer cell lines SW1990 and SW1990 after silencing STAT3 by siRNA were compared by gene chip technology to screen the downstream genes of STAT3. Results A total of 982 genes (2.55%) were screened out from 47 000 genes (representing 38 500 clear genes) according to the criteria of difference in significance, among which 592 genes were up-regulated and 592 were down-regulated Times the gene has 390. Drug resistance-related genes are: TopOIIα, TRAIL, significantly down-regulated cysteine-rich 61 (CYR61), Ras tumor gene family members (RAP1A), bcl-2-associated anti-apoptotic gene (BAG1), cystic fibrosis transmembrane conductance regulator (CFTR). Conclusions Pancreatic cancer drug resistance is the result of a multi-gene, multi-pathway interaction. After the STAT3 gene was silenced by siRNA, 6 resistance-related genes were changed. It will provide new clues for further research on the relationship between STAT3 and the drug resistance of pancreatic cancer and provide new ideas for the treatment of pancreatic cancer.