中华临床医师杂志（电子版）
中華臨床醫師雜誌（電子版）
중화림상의사잡지（전자판）
CHINESE JOURNAL OF CLINICIANS(ELECTRONIC VERSION)
2008年
7期
763-768
,共6页
蛋白激酶抑制剂%白血病,髓样%基因
蛋白激酶抑製劑%白血病,髓樣%基因
단백격매억제제%백혈병,수양%기인
Protein kinase inhibitors%Leukemia,myeloid%Genes
目的 应用基因表达谱芯片来检测丝氨酸/苏氨酸蛋白激酶Raf-1抑制剂对急性髓系白血病(AML)细胞基因表达的影响,试图进一步探讨丝氨酸/苏氨酸蛋白激酶Raf-1抑制剂抗白血病细胞增殖的机制.方法利用Cdna基因芯片研究10例成人AML,用两种不同的荧光素cy3和cy5通过逆转录反应将白血病细胞经丝氨酸/苏氨酸蛋白激酶Raf-1抑制剂作用前后的RNA分别标记成两种探针,并与基因表达谱芯片进行杂交,通过计算机扫描分析得出这些基因在经丝氨酸/苏氨酸蛋白激酶Raf-1抑制剂处理前后的表达差异.结果基因表达谱分析两次重复实验结果,最后筛选出包括与细胞凋亡、细胞周期等相关表达差异的基因共20条,其中12条表达上调,8条表达下调.结论结果提示丝氨酸/苏氨酸蛋白激酶Raf-1抑制剂抗成人急性粒细胞白血病的作用机制与抑制白血病细胞周期和诱导白血病细胞凋亡有很大关系.
目的 應用基因錶達譜芯片來檢測絲氨痠/囌氨痠蛋白激酶Raf-1抑製劑對急性髓繫白血病(AML)細胞基因錶達的影響,試圖進一步探討絲氨痠/囌氨痠蛋白激酶Raf-1抑製劑抗白血病細胞增殖的機製.方法利用Cdna基因芯片研究10例成人AML,用兩種不同的熒光素cy3和cy5通過逆轉錄反應將白血病細胞經絲氨痠/囌氨痠蛋白激酶Raf-1抑製劑作用前後的RNA分彆標記成兩種探針,併與基因錶達譜芯片進行雜交,通過計算機掃描分析得齣這些基因在經絲氨痠/囌氨痠蛋白激酶Raf-1抑製劑處理前後的錶達差異.結果基因錶達譜分析兩次重複實驗結果,最後篩選齣包括與細胞凋亡、細胞週期等相關錶達差異的基因共20條,其中12條錶達上調,8條錶達下調.結論結果提示絲氨痠/囌氨痠蛋白激酶Raf-1抑製劑抗成人急性粒細胞白血病的作用機製與抑製白血病細胞週期和誘導白血病細胞凋亡有很大關繫.
목적 응용기인표체보심편래검측사안산/소안산단백격매Raf-1억제제대급성수계백혈병(AML)세포기인표체적영향,시도진일보탐토사안산/소안산단백격매Raf-1억제제항백혈병세포증식적궤제.방법이용Cdna기인심편연구10례성인AML,용량충불동적형광소cy3화cy5통과역전록반응장백혈병세포경사안산/소안산단백격매Raf-1억제제작용전후적RNA분별표기성량충탐침,병여기인표체보심편진행잡교,통과계산궤소묘분석득출저사기인재경사안산/소안산단백격매Raf-1억제제처리전후적표체차이.결과기인표체보분석량차중복실험결과,최후사선출포괄여세포조망、세포주기등상관표체차이적기인공20조,기중12조표체상조,8조표체하조.결론결과제시사안산/소안산단백격매Raf-1억제제항성인급성립세포백혈병적작용궤제여억제백혈병세포주기화유도백혈병세포조망유흔대관계.
Objective The serine/threonine protein kinase( Raf-1) constitutive activation have been identified in a range of human tumors,including acute myelogenous leukemia(AML).The collective evidence suggests that Raf-1 is a viable anticancer drug target.We therefore targeted Raf-1 downstream of Ras using Raf-1 inhibitor that inhibit Raf-1 kinase activity in the treatment of AML and displayed potent antitumor and antiproliferative activity.The purposes of this study is to investigate the mechanism of anti-leukemia of Raf-1 inhibitor.Methods Experiments were carried out to study 10 adult AML patients by cDNA microarray.Total RNA from AML patients was isolated before and after Raf-1 inhibitor treatment.cDNA probes by RT-PCR were labeled with cy3 and cy5 fluorescence dyes,hybridized with cDNA microarray,and scanned for fluorescent intensity.The resulting images were quantitated by Axon Genepix software.Gene expression profiling after drug treatment were compared to pretreatment.Results Twenty genes related to apoptosis,cell cycle and others expressed different after the treatment of Raf-1 inhibitor,12 genes were up regulated,8 genes down regulated.Conclusions The mechanism of anti-leukemia proliferation of Raf-1 inhibitor is related to cell cycle inhibition and cell apoptosis induced by Raf-1 inhibitor.
