CAJ | 학술논문

目的研究磷酸化STAT3抑制剂Cucurbitacin Ⅰ阻断STAT3信号转导通路对人脑胶质瘤细胞系A172增殖和凋亡的影响并探讨机制.方法使用Cucurbitacin Ⅰ处理人脑胶质瘤细胞系A172,CCK-8方法检测细胞增殖状态,流式细胞仪检测细胞凋亡,Western blot检测STAT3磷酸化水平,RT-PCR检测STAT3下游基因C-myc、Survivin和Mcl-1的mRNA水平的改变.结果 Cucurbitacin Ⅰ作用于A172后,细胞增殖速度明显下降(P＜0.05);细胞凋亡比率显著升高;Western blot结果显示A172细胞中磷酸化STAT3(p705-STAT3)蛋白水平明显降低;C-myc、Survivin和Mcl-1在mRNA水平明显下降(P＜0.05).结论阻断STAT3信号转导通路可抑制脑胶质瘤细胞增殖,促进其凋亡;靶向STAT3信号转导通路的治疗策略可以作为胶质瘤治疗的一种新方法.
목적 연구린산화STAT3억제제Cucurbitacin Ⅰ조단STAT3신호전도통로대인뇌효질류세포계A172증식화조망적영향병탐토궤제.방법 사용Cucurbitacin Ⅰ처리인뇌효질류세포계A172,CCK-8방법검측세포증식상태,류식세포의검측세포조망,Western blot검측STAT3린산화수평,RT-PCR검측STAT3하유기인C-myc、Survivin화Mcl-1적mRNA수평적개변.결과 Cucurbitacin Ⅰ작용우A172후,세포증식속도명현하강(P＜0.05);세포조망비솔현저승고;Western blot결과현시A172세포중린산화STAT3(p705-STAT3)단백수평명현강저;C-myc、Survivin화Mcl-1재mRNA수평명현하강(P＜0.05).결론 조단STAT3신호전도통로가억제뇌효질류세포증식,촉진기조망;파향STAT3신호전도통로적치료책략가이작위효질류치료적일충신방법.
Objective To investigate the effects of blocking signal transducer and activator of transcription 3(STAT3)signaling pathway by phosphotyrosine STAT3 level inhibitor Cucurbitacin Ⅰ on the proliferation and apotosis of human glioma(cell line A172 in vitro.Methods A172 cells were treated with Cucurbitacin I.CCK-8 assay was used to measure cell growth rate.Cell apoptosis was detected by flow cytometry and measured by Annexin V binding and propidium iodide uptake.To analyze STAT3 levels,cells were examined bv Western blot,and the expression of STAT3 downstream genes(Survivin,c-myc and Mcl-1)were detected by RT-PCR.Results The proliferation of A172 cells decreased significantly after treatment for 24h(P＜0.05).while the apoptosis rate was increased.Further investigates indicated that Cucurbitacin Ⅰ reduced the level of phosphorylated STAT3(pSTAT3)in A172 cells and downregulated the expression of Survivin.C-myc and Mcl-1 mRNA obviously.Conclusion Cucurbitacin Ⅰ can obviously inhibit the proliferation and induce the apoptosis of the glioma cell line A172 via blocking activated STAT3.STAT3 may be a potential target in the treatment of glioma with constitutively activatied STAT3.