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Development of a STAT3 Reporter Prostate Cancer Cell Line for High Throughput Screening of STAT3 Activators and Inhibitors

机译:STAT3报告基因前列腺癌细胞系的开发用于高通量筛选STAT3激活剂和抑制剂

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摘要

STAT3 is constitutively activated in several cancers, including prostate cancer, and is therefore, a potential target for cancer therapy. DU-145 prostate cancer cells were stably co-transfected with STAT3 reporter and puromycin resistant plasmids to create a stable STAT3 reporter cell line that can be used for high throughput screening of STAT3 modulators. The applicability of this cell line was tested with two known activators and inhibitors of STAT3. As expected, EGF and IL-6 increased STAT3 reporter activity and enhanced the nuclear localization of phosphorylated STAT3 (pSTAT3); whereas Cucurbitacin I and AG490 decreased STAT3 reporter activity dose and time-dependently and reduced the localization of pSTAT3 in the nuclei of prostate cancer cells. Given the importance of STAT3 in cancer initiation and progression, the development of a stable STAT3 reporter cell line in prostate cancer cells provides a rapid, sensitive, and cost effective method for the screening of potential STAT3 modulators.
机译:STAT3在包括前列腺癌在内的多种癌症中被组成性激活,因此是癌症治疗的潜在靶标。将DU-145前列腺癌细胞与STAT3报告基因和嘌呤霉素抗性质粒稳定共转染,以创建稳定的STAT3报告细胞系,该细胞系可用于STAT3调节剂的高通量筛选。用两种已知的STAT3激活剂和抑制剂测试了该细胞系的适用性。正如预期的那样,EGF和IL-6增加了STAT3报告基因的活性,并增强了磷酸化STAT3(pSTAT3)的核定位。而葫芦素I和AG490降低了STAT3报告基因的活性剂量和时间依赖性,并减少了pSTAT3在前列腺癌细胞核中的定位。鉴于STAT3在癌症的发生和发展中的重要性,在前列腺癌细胞中稳定STAT3报告基因细胞系的开发提供了一种快速,灵敏且经济高效的方法来筛选潜在的STAT3调节剂。

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