中华生物医学工程杂志
中華生物醫學工程雜誌
중화생물의학공정잡지
CHINESE JOURNAL OF BIOMEDICAL ENGINEERING
2013年
4期
293-299
,共7页
鞠宝辉%黄宇婷%田菁%于虎%郝权
鞠寶輝%黃宇婷%田菁%于虎%郝權
국보휘%황우정%전정%우호%학권
卵巢肿瘤%肿瘤干细胞%基因表达谱%药物筛选试验,抗肿瘤
卵巢腫瘤%腫瘤榦細胞%基因錶達譜%藥物篩選試驗,抗腫瘤
란소종류%종류간세포%기인표체보%약물사선시험,항종류
Ovarian neoplasms%Neoplastic stem cells%Gene expression profile%Drug screening assays,antitumor
目的 综合分析卵巢癌中各干细胞特异性基因表达谱,发现其共同的表达特征,以期筛选具有逆转肿瘤细胞干细胞特性的小分子化合物.方法 从NCBI GEO数据库中获取卵巢癌细胞系、患者来源的卵巢癌干细胞与各非干性卵巢癌细胞的全基因组表达谱,进行整合比对分析,并以8例进展期卵巢癌细胞与正常卵巢上皮细胞的差异基因表达谱为校正,获得差异表达基因.利用GeneSifter软件解析卵巢癌细胞的干性特征并建立分子标签,使用连通图法筛选具有逆转此类分子标签的小分子化合物.结果 进展期卵巢癌患者来源的卵巢癌细胞相比正常人卵巢上皮细胞、卵巢癌细胞系OVCAR-3来源的多细胞球相比OVCAR-3细胞、卵巢癌细胞系IGROV1来源的侧群细胞相比非侧群细胞、进展期卵巢癌患者腹水细胞来源的侧群细胞相比腹水总体细胞差异表达的基因数分别为6053、6495、1347、509个,均满足差异基因表达在1.5倍以上且t检验P值＜0.05.其中NGFI-A结合蛋白1(NAB1)等为共同上调的关键基因,S蛋白1(PROS1)、雌激素介导的乳腺癌生长调节因子1(GREB1)、Kruppel相似因子9(KLF9)和线粒体肿瘤抑制因子1(MTUS1)等为共同下调基因.筛选出SC-560、disulfiram、thapsigargin、esculetin、cinchonine等18种小分子化合物具有逆转卵巢癌细胞干性的潜在药理特性.结论 初步揭示了各卵巢癌细胞中共有的干性差异表达基因及其特异调控网络,为筛选卵巢癌干细胞靶向药物提供了依据.
目的 綜閤分析卵巢癌中各榦細胞特異性基因錶達譜,髮現其共同的錶達特徵,以期篩選具有逆轉腫瘤細胞榦細胞特性的小分子化閤物.方法 從NCBI GEO數據庫中穫取卵巢癌細胞繫、患者來源的卵巢癌榦細胞與各非榦性卵巢癌細胞的全基因組錶達譜,進行整閤比對分析,併以8例進展期卵巢癌細胞與正常卵巢上皮細胞的差異基因錶達譜為校正,穫得差異錶達基因.利用GeneSifter軟件解析卵巢癌細胞的榦性特徵併建立分子標籤,使用連通圖法篩選具有逆轉此類分子標籤的小分子化閤物.結果 進展期卵巢癌患者來源的卵巢癌細胞相比正常人卵巢上皮細胞、卵巢癌細胞繫OVCAR-3來源的多細胞毬相比OVCAR-3細胞、卵巢癌細胞繫IGROV1來源的側群細胞相比非側群細胞、進展期卵巢癌患者腹水細胞來源的側群細胞相比腹水總體細胞差異錶達的基因數分彆為6053、6495、1347、509箇,均滿足差異基因錶達在1.5倍以上且t檢驗P值＜0.05.其中NGFI-A結閤蛋白1(NAB1)等為共同上調的關鍵基因,S蛋白1(PROS1)、雌激素介導的乳腺癌生長調節因子1(GREB1)、Kruppel相似因子9(KLF9)和線粒體腫瘤抑製因子1(MTUS1)等為共同下調基因.篩選齣SC-560、disulfiram、thapsigargin、esculetin、cinchonine等18種小分子化閤物具有逆轉卵巢癌細胞榦性的潛在藥理特性.結論 初步揭示瞭各卵巢癌細胞中共有的榦性差異錶達基因及其特異調控網絡,為篩選卵巢癌榦細胞靶嚮藥物提供瞭依據.
목적 종합분석란소암중각간세포특이성기인표체보,발현기공동적표체특정,이기사선구유역전종류세포간세포특성적소분자화합물.방법 종NCBI GEO수거고중획취란소암세포계、환자래원적란소암간세포여각비간성란소암세포적전기인조표체보,진행정합비대분석,병이8례진전기란소암세포여정상란소상피세포적차이기인표체보위교정,획득차이표체기인.이용GeneSifter연건해석란소암세포적간성특정병건립분자표첨,사용련통도법사선구유역전차류분자표첨적소분자화합물.결과 진전기란소암환자래원적란소암세포상비정상인란소상피세포、란소암세포계OVCAR-3래원적다세포구상비OVCAR-3세포、란소암세포계IGROV1래원적측군세포상비비측군세포、진전기란소암환자복수세포래원적측군세포상비복수총체세포차이표체적기인수분별위6053、6495、1347、509개,균만족차이기인표체재1.5배이상차t검험P치＜0.05.기중NGFI-A결합단백1(NAB1)등위공동상조적관건기인,S단백1(PROS1)、자격소개도적유선암생장조절인자1(GREB1)、Kruppel상사인자9(KLF9)화선립체종류억제인자1(MTUS1)등위공동하조기인.사선출SC-560、disulfiram、thapsigargin、esculetin、cinchonine등18충소분자화합물구유역전란소암세포간성적잠재약리특성.결론 초보게시료각란소암세포중공유적간성차이표체기인급기특이조공망락,위사선란소암간세포파향약물제공료의거.
Objective To comprehensively analyze the specific gene expression profile of stem cells in ovarian cancer and the common features,thus to identify the small molecules that may avert the stemness of ovarian cancer cells.Methods The genome-wide expression profiles of ovarian cancer cell lines,ovarian cancer stem cells (OVCSCs) from patients with ovarian cancer and non-stem cancer cells derived from NCBI GEO bank were collected and compared.This was followed by adjustment with the cancer cells derived from 8 patients with progressive ovarian cancer and normal ovarian epithelial cells to capture the differential expression genes for subsequent interpretation of the sterness and establishment of molecular tags via GeneSifter software,and to screen small molecules that may suppress the expression of molecular tags of OVCSCs by using connectivity map.Results The number of genes with differential expression was 6053 for ovarian cancer cells derived from progressive ovarian cancer compared with normal ovarian epithelial cells,6495 for multiple cellular spheroid cells derived from the OVCAR-3 cells line compared with OVCAR-3 cells,1347 for the side population cells compared with non-side population cells of ovarian cancer cell line IGROV 1,and 509 for the side population cells compared with the total cell populations derived from the ascites in patients with progressive ovarian cancer (all differences ＞1.5 fold,t test P value＜O.05).Among above genes,the NGFI-A binding protein 1 (NAB1) was the key up-regulated gene,whilst the protein S alpha (PROS1),growth regulation by estrogen in breast cancer 1 (GREB1),Kruppel-like factor 9 (KLF9) and mitochondrial tumor suppressor 1 (MTUS1) genes were down-regulated.A total of 18 small molecules with potential pharmacological properties of averting the stemness of OVCSCs,i.e.SC-560,disulfiram,thapsigargin,esculetin and cinchonine,were identified.Conclusion The primary elucidation of stemness genes with differential expression in ovarian cancer and their specific regulation networks may offer the rationale for identifying targeted drugs for OVCSCs.
