上海交通大学学报（医学版）
上海交通大學學報（醫學版）
상해교통대학학보（의학판）
JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY(MEDICAL SCIENCE)
2009年
10期
1187-1190
,共4页
王鸣明%邹丽芳%窦红菊%朱琦%任志宏%胡钧培
王鳴明%鄒麗芳%竇紅菊%硃琦%任誌宏%鬍鈞培
왕명명%추려방%두홍국%주기%임지굉%호균배
砷剂%骨髓瘤%SOCS-1基因%JAK/STAT3%细胞周期
砷劑%骨髓瘤%SOCS-1基因%JAK/STAT3%細胞週期
신제%골수류%SOCS-1기인%JAK/STAT3%세포주기
arsenic trioxide%myeloma%SOCS-1%JAK/STAT3%cell cycle
目的 研究三氧化二砷(AS_2O_3)诱导人骨髓瘤细胞U266、RPMI8226细胞内 JAK/STAT3信号转导通路抑制与细胞增殖之间存在的关系.方法 采用MTT法观察AS_2O_3对骨髓瘤细胞作用的半数抑制浓度(IC_(50)),流式细胞技术检测AS_2O_3作用前后细胞周期的改变情况,甲基化特异性PCR法检测AS_2O_3作用前后骨髓瘤细胞内SOCS-1基因甲基化状态的变化,Western blotting法检测AS_2O_3作用前后磷酸化STAT3蛋白的表达差异.结果 AS_2O_3作用72 h后,骨髓瘤细胞U266、RPMI8226细胞内磷酸化STAT3蛋白表达水平明显降低,同时伴随SOCS-1基因启动子区CpG岛甲基化程度明显减弱至消失,细胞增殖发生G_0/G_1期阻滞,上述三者变化均与AS_2O_3浓度呈正相关(r=0.85,P<0.05).结论 AS_2O_3可诱导骨髓瘤细胞增殖受抑,与AS_2O_3诱导细胞内JAK/STAT3信号转导通路抑制存在一定关系,且与细胞内SOCS-1基因甲基化状态改变相关.
目的 研究三氧化二砷(AS_2O_3)誘導人骨髓瘤細胞U266、RPMI8226細胞內 JAK/STAT3信號轉導通路抑製與細胞增殖之間存在的關繫.方法 採用MTT法觀察AS_2O_3對骨髓瘤細胞作用的半數抑製濃度(IC_(50)),流式細胞技術檢測AS_2O_3作用前後細胞週期的改變情況,甲基化特異性PCR法檢測AS_2O_3作用前後骨髓瘤細胞內SOCS-1基因甲基化狀態的變化,Western blotting法檢測AS_2O_3作用前後燐痠化STAT3蛋白的錶達差異.結果 AS_2O_3作用72 h後,骨髓瘤細胞U266、RPMI8226細胞內燐痠化STAT3蛋白錶達水平明顯降低,同時伴隨SOCS-1基因啟動子區CpG島甲基化程度明顯減弱至消失,細胞增殖髮生G_0/G_1期阻滯,上述三者變化均與AS_2O_3濃度呈正相關(r=0.85,P<0.05).結論 AS_2O_3可誘導骨髓瘤細胞增殖受抑,與AS_2O_3誘導細胞內JAK/STAT3信號轉導通路抑製存在一定關繫,且與細胞內SOCS-1基因甲基化狀態改變相關.
목적 연구삼양화이신(AS_2O_3)유도인골수류세포U266、RPMI8226세포내 JAK/STAT3신호전도통로억제여세포증식지간존재적관계.방법 채용MTT법관찰AS_2O_3대골수류세포작용적반수억제농도(IC_(50)),류식세포기술검측AS_2O_3작용전후세포주기적개변정황,갑기화특이성PCR법검측AS_2O_3작용전후골수류세포내SOCS-1기인갑기화상태적변화,Western blotting법검측AS_2O_3작용전후린산화STAT3단백적표체차이.결과 AS_2O_3작용72 h후,골수류세포U266、RPMI8226세포내린산화STAT3단백표체수평명현강저,동시반수SOCS-1기인계동자구CpG도갑기화정도명현감약지소실,세포증식발생G_0/G_1기조체,상술삼자변화균여AS_2O_3농도정정상관(r=0.85,P<0.05).결론 AS_2O_3가유도골수류세포증식수억,여AS_2O_3유도세포내JAK/STAT3신호전도통로억제존재일정관계,차여세포내SOCS-1기인갑기화상태개변상관.
Objective To explore the possible relationship between alteration of cell cycle and JAK/STAT3 signal transduction pathway inhibition induced by arsenic trioxide (As_2O_3,) in myeloma cell lines U266 and RPMI8226 in vitro. Methods Multiple myeloma cell lines U266 and RPMI8226 were used as in vitro models. The influence of AS_2O_3 on myeloma cells were evaluated by MTT assay and flow cytometry. Meanwhile, methylation specific PCR and Western blotting were employed to detect the methylation status of gene SOCS-1 and protein expression level of P-STAT3 in these cells after AS_2O_3 treatment. Results AS_2O_3 significantly inhibited the growth of U266 and RPMI8226 cells in a dose-dependent manner. Furthermore, cell cycle was arrested at G0/G1 phase with inhibition of protein expression level of P-STAT3 and SOCS-1 gene demethylation after exposure to As_2O_3 for 72 h( r = 0. 85, P < 0.05). Conclusion AS_2O_3 could induce the alteration of cell cycle which might be related to JAK/STAT3 signal transduction pathway inhibition and SOCS-1 demethylation in myeloma cell lines. The study puts forward a new idea of AS_2 O_3 treatment in multiple myeloma.
