CAJ | 학술논문

目的探讨两面神激酶2/信号转导及转录活化因子3(JAK2/STAT3)信号通路与非小细胞肺癌(NSCLC)微血管形成之间的关系,以及干预JAK2/STAT3信号通路对血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)表达的影响.方法应用免疫组织化学方法检测68例NSCLC和27例正常肺组织中P-JAK2、P-STAT3的表达及微血管密度(MVD)值,并分析与各临床、病理参数的关系;使用不同浓度的JAK2抑制剂AG490处理人肺腺癌细胞A549后,MTF法检测细胞的增殖状态,Western blot法检测JAK2/STAT3信号通路的活化状态,RT-PCR法检测AG490对VEGF、bFGF mRNA的表达的影响;在A549细胞中转染STAT3小干扰RNA(siRNA),Western blot法检测STAT3及磷酸化-STAT3(P-STAT3)蛋白的表达,RT-PCR法检测VEGF、bFGF mRNA的表达.结果 NSCLC的免疫组化结果显示JAK2/STAT3信号通路的活化与MVD计数正相关(P＜0.05);使用AG490和STAT3 siRNA干预该通路的活化后,VEGF和bFGF mRNA的表达下降(P＜0.05).结论 JAK2/STAT3信号转导通路与肺癌微血管生成密切相关,阻断该通路的活化能抑制血管生成相关因子的表达,提示JAK2/STAT3信号通路是抑制肺癌微血管生成的重要靶点.
목적 탐토량면신격매2/신호전도급전록활화인자3(JAK2/STAT3)신호통로여비소세포폐암(NSCLC)미혈관형성지간적관계,이급간예JAK2/STAT3신호통로대혈관내피생장인자(VEGF)、감성성섬유세포생장인자(bFGF)표체적영향.방법 응용면역조직화학방법검측68례NSCLC화27례정상폐조직중P-JAK2、P-STAT3적표체급미혈관밀도(MVD)치,병분석여각림상、병리삼수적관계;사용불동농도적JAK2억제제AG490처리인폐선암세포A549후,MTF법검측세포적증식상태,Western blot법검측JAK2/STAT3신호통로적활화상태,RT-PCR법검측AG490대VEGF、bFGF mRNA적표체적영향;재A549세포중전염STAT3소간우RNA(siRNA),Western blot법검측STAT3급린산화-STAT3(P-STAT3)단백적표체,RT-PCR법검측VEGF、bFGF mRNA적표체.결과 NSCLC적면역조화결과현시JAK2/STAT3신호통로적활화여MVD계수정상관(P＜0.05);사용AG490화STAT3 siRNA간예해통로적활화후,VEGF화bFGF mRNA적표체하강(P＜0.05).결론 JAK2/STAT3신호전도통로여폐암미혈관생성밀절상관,조단해통로적활화능억제혈관생성상관인자적표체,제시JAK2/STAT3신호통로시억제폐암미혈관생성적중요파점.
Objective To investigate the relationship between janus kinase2/signal transducer and activator of transcription 3 (JAK2/STAT3 ) signaling pathway and angiogenesis in non-small cell lung cancer (NSCLC) and explore the effects on the mRNA expression of vascular endothelial growth factor (VEGF)and basic fibroblast growth factor (bFGF) by blocking JAK2/STAT3 signaling pathway.Methods Immunohistochemistry was used to determine the expression of P-JAK2,P-STAT3 and microvessel density (MVD) in 68 NSCLC tissues and 27 normal lung tissues.And the relationship with their clinical pathological features was analyzed.Human lung cancer A549 cells were treated with different concentrations of AG490.Cell proliferation was measured by MTF assay.Western blot was performed to detect the activation of JAK2/STAT3 signaling pathway.The mRNA expressions of VEGF and bFGF were determined by RT-PCR (reverse transcription-polymerase chain reaction).A549 cells were transfected with STAT3 siRNA.And the protein of STAT3,Phos-STAT3 (P-STAT3) and mRNA levels of VEGF and bFGF were detected.Results The activation of JAK2/STAT3 signaling pathway was closely related to MVD in NSCLC.AG490 and STAT3 siRNA could block the JAK2/STAT3 signaling pathway and down-regulated the mRNA expressions of VEGF and bFGF in lung cancer cells.Conclusion JAK2/STAT3 signaling pathway plays an important role in the angiogenesis of NSCLC.Blocking this pathway may inhibit the expression of angiogenic cytokines.JAK2/STAT3 signaling pathway may be a critical therapeutic target for the treatment of angiogenesis in NSCLC.