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
11期
1316-1319
,共4页
周立宇%张征%应韶旭%李晓%常春康%贺琪%浦权
週立宇%張徵%應韶旭%李曉%常春康%賀琪%浦權
주립우%장정%응소욱%리효%상춘강%하기%포권
肿瘤坏死因子相关凋亡诱导配体%凋亡%白血病
腫瘤壞死因子相關凋亡誘導配體%凋亡%白血病
종류배사인자상관조망유도배체%조망%백혈병
tumor necrosis factor-related apoptosis-inducing ligand%apoptosis%leukemia
目的 探讨bexarotene联合肿瘤坏死因子相关凋亡诱导配体(TRAIL)对白血病细胞株KG1a凋亡的影响,并初步探讨其作用机制.方法 取对数生长期KG1a,根据不同处理方式分为TRAIL组、bexarotene组、300 ng/mL TRAIL联合bexarotene组和2.0 μmol/L bexaroten联合TRAIL组.流式细胞仪检测各组细胞凋亡率.以先加bexarotene或TRAIL孵育,后加TRAIL或bexarotene处理设计序贯实验,流式细胞仪检测细胞凋亡率.Western blotting分析KG1a细胞型自杀相关因子(Fas)相关死亡域样白介素-1β转换酶抑制蛋白(c-FLIP)表达变化.结果 TRAIL和bexarotene组的各浓度组间(bexarotene 2.0 μmol/L除外)细胞凋亡率比较,差异无统计学意义(P>0.05);两联合用药组的细胞凋亡率均明显高于相应浓度的TRAIL组和bexarotene组(P<0.01).序贯实验表明,bexarotene具有逆转 KG1a对TRAIL耐药的作用(P<0.001).与2.0 μmol/L bexarotene 或300 ng/mL TRAIL 单独用药比较,两者联合应用能显著下调c-FLIP表达(P<0.05).结论 Bexarotene能显著增强TRAIL对KG1a的诱导凋亡作用,下调c-FLIP表达是协同作用的可能机制.
目的 探討bexarotene聯閤腫瘤壞死因子相關凋亡誘導配體(TRAIL)對白血病細胞株KG1a凋亡的影響,併初步探討其作用機製.方法 取對數生長期KG1a,根據不同處理方式分為TRAIL組、bexarotene組、300 ng/mL TRAIL聯閤bexarotene組和2.0 μmol/L bexaroten聯閤TRAIL組.流式細胞儀檢測各組細胞凋亡率.以先加bexarotene或TRAIL孵育,後加TRAIL或bexarotene處理設計序貫實驗,流式細胞儀檢測細胞凋亡率.Western blotting分析KG1a細胞型自殺相關因子(Fas)相關死亡域樣白介素-1β轉換酶抑製蛋白(c-FLIP)錶達變化.結果 TRAIL和bexarotene組的各濃度組間(bexarotene 2.0 μmol/L除外)細胞凋亡率比較,差異無統計學意義(P>0.05);兩聯閤用藥組的細胞凋亡率均明顯高于相應濃度的TRAIL組和bexarotene組(P<0.01).序貫實驗錶明,bexarotene具有逆轉 KG1a對TRAIL耐藥的作用(P<0.001).與2.0 μmol/L bexarotene 或300 ng/mL TRAIL 單獨用藥比較,兩者聯閤應用能顯著下調c-FLIP錶達(P<0.05).結論 Bexarotene能顯著增彊TRAIL對KG1a的誘導凋亡作用,下調c-FLIP錶達是協同作用的可能機製.
목적 탐토bexarotene연합종류배사인자상관조망유도배체(TRAIL)대백혈병세포주KG1a조망적영향,병초보탐토기작용궤제.방법 취대수생장기KG1a,근거불동처리방식분위TRAIL조、bexarotene조、300 ng/mL TRAIL연합bexarotene조화2.0 μmol/L bexaroten연합TRAIL조.류식세포의검측각조세포조망솔.이선가bexarotene혹TRAIL부육,후가TRAIL혹bexarotene처리설계서관실험,류식세포의검측세포조망솔.Western blotting분석KG1a세포형자살상관인자(Fas)상관사망역양백개소-1β전환매억제단백(c-FLIP)표체변화.결과 TRAIL화bexarotene조적각농도조간(bexarotene 2.0 μmol/L제외)세포조망솔비교,차이무통계학의의(P>0.05);량연합용약조적세포조망솔균명현고우상응농도적TRAIL조화bexarotene조(P<0.01).서관실험표명,bexarotene구유역전 KG1a대TRAIL내약적작용(P<0.001).여2.0 μmol/L bexarotene 혹300 ng/mL TRAIL 단독용약비교,량자연합응용능현저하조c-FLIP표체(P<0.05).결론 Bexarotene능현저증강TRAIL대KG1a적유도조망작용,하조c-FLIP표체시협동작용적가능궤제.
Objective To explore the effects and mechanism of bexarotene in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on apoptosis of leukemic cell line KG1a. Methods KG1a cells at logarithmic growth phase were obtained, and were divided into TRAIL group, bexarotene group, 300 ng/mL TRAIL in combination with bexarotene group and 2.0 μmol/L bexaroten in combination with TRAIL group. Cell apoptosis rate was detected in each group by flow cytometry. Flow cytometry was also employed to determine the apoptosis rates of KG1a cells after treatment with bexarotene and TRAIL in different sequences. The expression of Fas associated death domain-like IL-1 beta converting enzyme inhibitory protein (c-FLIP) was detected by Western blotting. Results There was no significant difference in cell apoptosis rates between TRAIL group and bexarotene group of each concentration (except for bexarotene 2.0 μmol/L) (P > 0.05). The cell apoptosis rates of 300 ng/mL TRAIL in combination with bexarotene group and 2.0 μmol/L bexaroten in combination with TRAIL group were significantly higher than those in TRAIL group and bexarotene group of each corresponding concentration (P <0.01). Sequential analysis revealed that bexarotene could reverse the resistance of KG1a cells to TRAIL (P < 0.001). Compared with single use of 2.0 μmol/L bexarotene or 300 ng/mL TRAIL, combination use could significantly down-regulated the expression of c-FLIP (P < 0.05). Conclusion Bexarotene can significantly enhance the apoptosis of KG1a cells induced by TRAIL, which may be attributed to the down-regulation of c-FLIP expression.
