国际免疫学杂志
國際免疫學雜誌
국제면역학잡지
INTERNATIONAL JOURNAL OF IMMUNOLOGY
2012年
5期
403-406
,共4页
罗晶珠%赵经慧%卢润章%梁丽
囉晶珠%趙經慧%盧潤章%樑麗
라정주%조경혜%로윤장%량려
三氧化二砷%伊马替尼耐药%生长抑制%突变%bcr/abl
三氧化二砷%伊馬替尼耐藥%生長抑製%突變%bcr/abl
삼양화이신%이마체니내약%생장억제%돌변%bcr/abl
Arsenic trioxide%IM-resistant%Growth inhibition%Mutant%bcr/abl
目的 探讨三氧化二砷( ATO)对伊马替尼(IM)产生耐药性的慢性粒细胞性白血病(CML)细胞是否具有抑制细胞生长的作用.方法 小鼠髓系造血细胞株32D细胞经处理使其变为表达p210Bcr-Abl的32Dp210细胞,以此作为野生型细胞.32Dp210和伊马替尼耐药细胞株32Dp210T315I分别在含有10％ FBS,2％ L-glutamine和1％ Penicillin-Streptomycin的RPMI1640和IMDM培养体系中培养.细胞株分别在不同浓度的三氧化二砷、伊马替尼作为对照的没有药物作用的培养体系中培养.在24h和48 h后,MTT实验检测细胞增殖,Annexin-V staining实验检测细胞凋亡.结果 在体外试验中,我们发现三氧化二砷对32Dp210和32Dp210T315I具有剂量依赖的抑制作用,对32Dp210T315I细胞的抑制比对32Dp210细胞更为有效.三氧化二砷对32Dp210T315I细胞的50％抑制浓度(IC50)是1μmol/L,远低于32Dp210的IC50值(4μmol/L).2μmol/L三氧化二砷可以明显诱导约90％的32Dp210T315I细胞凋亡,比32Dp210的凋亡率(30％)高很多.结论 ATO具有作为一种生长抑制剂和诱导伊马替尼耐药细胞凋亡的特性,也使其成为一种新的治疗伊马替尼耐药CML患者的治疗途径.
目的 探討三氧化二砷( ATO)對伊馬替尼(IM)產生耐藥性的慢性粒細胞性白血病(CML)細胞是否具有抑製細胞生長的作用.方法 小鼠髓繫造血細胞株32D細胞經處理使其變為錶達p210Bcr-Abl的32Dp210細胞,以此作為野生型細胞.32Dp210和伊馬替尼耐藥細胞株32Dp210T315I分彆在含有10％ FBS,2％ L-glutamine和1％ Penicillin-Streptomycin的RPMI1640和IMDM培養體繫中培養.細胞株分彆在不同濃度的三氧化二砷、伊馬替尼作為對照的沒有藥物作用的培養體繫中培養.在24h和48 h後,MTT實驗檢測細胞增殖,Annexin-V staining實驗檢測細胞凋亡.結果 在體外試驗中,我們髮現三氧化二砷對32Dp210和32Dp210T315I具有劑量依賴的抑製作用,對32Dp210T315I細胞的抑製比對32Dp210細胞更為有效.三氧化二砷對32Dp210T315I細胞的50％抑製濃度(IC50)是1μmol/L,遠低于32Dp210的IC50值(4μmol/L).2μmol/L三氧化二砷可以明顯誘導約90％的32Dp210T315I細胞凋亡,比32Dp210的凋亡率(30％)高很多.結論 ATO具有作為一種生長抑製劑和誘導伊馬替尼耐藥細胞凋亡的特性,也使其成為一種新的治療伊馬替尼耐藥CML患者的治療途徑.
목적 탐토삼양화이신( ATO)대이마체니(IM)산생내약성적만성립세포성백혈병(CML)세포시부구유억제세포생장적작용.방법 소서수계조혈세포주32D세포경처리사기변위표체p210Bcr-Abl적32Dp210세포,이차작위야생형세포.32Dp210화이마체니내약세포주32Dp210T315I분별재함유10％ FBS,2％ L-glutamine화1％ Penicillin-Streptomycin적RPMI1640화IMDM배양체계중배양.세포주분별재불동농도적삼양화이신、이마체니작위대조적몰유약물작용적배양체계중배양.재24h화48 h후,MTT실험검측세포증식,Annexin-V staining실험검측세포조망.결과 재체외시험중,아문발현삼양화이신대32Dp210화32Dp210T315I구유제량의뢰적억제작용,대32Dp210T315I세포적억제비대32Dp210세포경위유효.삼양화이신대32Dp210T315I세포적50％억제농도(IC50)시1μmol/L,원저우32Dp210적IC50치(4μmol/L).2μmol/L삼양화이신가이명현유도약90％적32Dp210T315I세포조망,비32Dp210적조망솔(30％)고흔다.결론 ATO구유작위일충생장억제제화유도이마체니내약세포조망적특성,야사기성위일충신적치료이마체니내약CML환자적치료도경.
Objective To explore the effect of arsenic trioxide (ATO) on the growth inhibition of imatinib(IM)-resistant CML cell lines in vitro.Methods Mouse 32D cells expressing p210bcr/abl are used as wild type cells.The wide type cells and IM-resistant cell line 32Dp210T315Icells were cultured with 10％ FBS,2％ L-glutamine and 1％ Penicillin-Streptomycin RPMI1640 or IMDM.MTT assay was used to evaluate the efficacy of IM and ATO treatment for cell growth in wild-type cell line,32Dp210 and IM-resistant cell line 32Dp210T315I ;Apoptosis was analysied by flow cytometer with Annexin V & PI staining.Results In vitro,ATO significantly inhibited the growth of IM-resistant cells compared with wild-type bcr/abl cells.Fifty percentage inhibitory concentration (IC50) values( 1 μ mol/L) of ATO on IM-resistant cells 32Dp210T315I was up to 4 fold lower than that of wile-type bcr/abl cells (4 μmol/L).2μmol/L ATO induced apoptosis in 90％ IM-resistant cell 32Dp210T315I,which significantly higher than that in wide type bcr/abl cells.Conclusion Our results indicate that ATO remarkably inhibited cell growth and induced apoptosis of IM-resistant cell line 32Dp210T315I in vitro.These results suggested that ATO could be a potential therapeutic agent against IM-resistant CML patients.
