【摘要】 目的:探讨新型信号转录和激活因子3（STAT3）抑制剂WP1066对BRAF^V600E突变型甲状腺癌BCPAP细胞的作用及分子机制。方法:WP1066处理BCPAP细胞,CCK-8法测定存活率并计算半抑制浓度(IC₅₀);流式细胞术检测细胞周期和凋亡;Western Blot测定STAT3的活化水平及其下游Cleaved Caspase-3、Cleaved PARP、p21、p53、cyclin D1、BCL-XL和BAX的水平。结果:WP1066可抑制BCPAP细胞的增殖并呈浓度依赖性,48hIC₅₀为2.7μmol/L;WP1066诱导BCPAP细胞G1期阻滞并诱导细胞凋亡;WP1066可抑制STAT3的磷酸化,拮抗cyclin D1、BCL-XL的表达,促进Cleaved Caspase-3、Cleaved PARP、p21、p53和BAX的表达。结论:WP1066通过抑制STAT3信号通路,拮抗甲状腺癌BCPAP细胞增殖,并诱导G1期阻滞和凋亡。更多还原

【Abstract】 Objective:To investigate the effect and molecular mechanism of WP1066 on BRAF^V600E mutant thyroid carcinoma cell line BCPAP.Methods:Following pretreatment with WP1066,the proliferation of BCPAP cells was investigated by CCK-8 assay,and then the IC₅₀ value was calculated.The cell cycle and apoptosis rate were evaluated by the flow cytometry.The levels of signal transducer and activator of transcription 3（STAT3）and its downstream proteins,including Cleaved Caspase-3,Cleaved PARP,p21,p53,cyclin D1,BCL-XL and BAX,were measured by Western Blot.Results: WP1066 inhibited the proliferation of BCPAP cells,and the IC₅₀ of WP1066 for 48 hwas 2.7μmol/L.WP1066 induced G1 phase arrest and apoptosis of BCPAP cells.In addition,WP1066 suppressed STAT3 phosphorylation,and downregulated the expression of cyclin D1 and BCL-XL,but up-regulated the expression of Cleaved Caspase-3,Cleaved PARP,p21,p53 and BAX.Conclusion:WP1066 could suppress BCPAP cells proliferation,induce G1 phase arrest and apoptosis by inhibiting transduction of STAT3 pathway.更多还原