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首页> 外文期刊>Cancer science. >RNA interference-mediated signal transducers and activators of transcription 3 gene silencing inhibits invasion and metastasis of human pancreatic cancer cells.
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RNA interference-mediated signal transducers and activators of transcription 3 gene silencing inhibits invasion and metastasis of human pancreatic cancer cells.

机译：RNA干扰介导的信号转导子和转录激活子3基因沉默抑制人类胰腺癌细胞的侵袭和转移。

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摘要

Signal transducers and activators of transcription-3 (STAT3), a central cytoplasmic transcription factor, is frequently overexpressed and constitutively activated by tyrosine during malignant transformation. The overexpression and phosphorylation of STAT3 in pancreatic cancer has been described only recently, but the roles and mechanism still remain unclear. In this study, we elucidate the significance of the STAT3 signaling pathway in metastatic potentials of pancreatic cancer. We stably silence the expression of the STAT3 and p-STAT3 by using RNA interference (RNAi) in the pancreatic cancer cell line SW1990, and then reduce its invasion capacity in vitro and metastasis capacity in vivo compared to parental cells or cells tansfected with a control vector. Furthermore, silencing SW1990 cells with the STAT3 gene by RNAi also led to a decrease of matrix metalloproteinases-2 (MMP-2) and vascular endothelial growth factor (VEGF) at the mRNA and protein level. Collectively, these studies suggest that activation of the STAT3 signaling pathway plays an important role in the progression of pancreatic cancer, and that silence of the STAT3 gene with RNAi may be a useful anti-invasive therapeutic option in pancreatic cancer.
机译：信号转导和转录激活因子（STAT3）（一种中央细胞质转录因子）在恶性转化过程中经常被酪氨酸过度表达并组成性激活。 STAT3在胰腺癌中的过表达和磷酸化只是最近才有报道，但其作用和机制仍不清楚。在这项研究中，我们阐明了STAT3信号通路在胰腺癌转移潜力中的意义。我们通过使用RNA干扰（RNAi）在胰腺癌细胞系SW1990中稳定沉默STAT3和p-STAT3的表达，然后与亲本细胞或转染对照的细胞相比，降低其体外侵袭能力和体内转移能力向量。此外，RNAi使STAT3基因使SW1990细胞沉默，也导致基质金属蛋白酶2（MMP-2）和血管内皮生长因子（VEGF）在mRNA和蛋白质水平上降低。总体而言，这些研究表明，STAT3信号通路的激活在胰腺癌的进展中起重要作用，而用RNAi沉默STAT3基因可能是胰腺癌的一种有用的抗侵袭性治疗选择。

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