CAJ | 학술논문

目的观察甲基化抑制剂5-氮杂胞苷(5-aza-CdR)联合伊马替尼对人胃肠间质瘤(GIST)细胞GIST 882生长、运动、侵袭和凋亡的影响.方法 MTT法检测不同浓度5-aza-CdR、伊马替尼及双药联合作用对GIST882细胞生长情况的影响；平板克隆形成实验检测克隆形成数;迁徙运动及侵袭实验观察药物干预对细胞运动和侵袭能力的影响;流式细胞术检测各组细胞周期和凋亡的情况.结果 5-aza-CdR与伊马替尼对GIST882细胞均有较强的抑制作用,此作用呈浓度和时间依赖性;两药联用的抑制率较单独应用明显增高(P＜0.05).药物作用48 h时,5-aza-CdR组(1000 μg/L)的细胞凋亡率为(11.7±1.2)％,伊马替尼组(100 μmol/L)则为(14.6±0.8)％,与对照组(2.8±0.3)％相比,差异有统计学意义(P=0.000).联合组细胞凋亡率为(19.4±1.1)％,明显高于单药组(与5-aza-CdR组相比,P=0.000;与伊马替尼组相比,P=0.013).5-aza-CdR可使GIST882 G0/G1期比例增加,S期比例降低,伊马替尼组及联合用药组对细胞周期的改变不明显.结论去甲基化药物有望成为GIST药物治疗中单独或联合用药的新选择.
목적 관찰갑기화억제제5-담잡포감(5-aza-CdR)연합이마체니대인위장간질류(GIST)세포GIST 882생장、운동、침습화조망적영향.방법 MTT법검측불동농도5-aza-CdR、이마체니급쌍약연합작용대GIST882세포생장정황적영향；평판극륭형성실험검측극륭형성수;천사운동급침습실험관찰약물간예대세포운동화침습능력적영향;류식세포술검측각조세포주기화조망적정황.결과 5-aza-CdR여이마체니대GIST882세포균유교강적억제작용,차작용정농도화시간의뢰성;량약련용적억제솔교단독응용명현증고(P＜0.05).약물작용48 h시,5-aza-CdR조(1000 μg/L)적세포조망솔위(11.7±1.2)％,이마체니조(100 μmol/L)칙위(14.6±0.8)％,여대조조(2.8±0.3)％상비,차이유통계학의의(P=0.000).연합조세포조망솔위(19.4±1.1)％,명현고우단약조(여5-aza-CdR조상비,P=0.000;여이마체니조상비,P=0.013).5-aza-CdR가사GIST882 G0/G1기비례증가,S기비례강저,이마체니조급연합용약조대세포주기적개변불명현.결론 거갑기화약물유망성위GIST약물치료중단독혹연합용약적신선택.
Objective To investigate the impact of 5-aza-2'-deoxycytidine (5-aza-CdR) combined with imatinib on the proliferation,motility,invasion,and apoptosis of gastrointestinal stromal tumors (GIST) cells in vitro.Methods MTT assay was used to investigate the effect of the two agents on proliferation of GIST882.Plate colony forming assay was used to determine the number of colonyforming.Motility and invasion abilities were tested to evaluate the inhibitory effect of each agent.Flow cytometry was used to observe apoptosis and cell cycle. Results 5-aza-CdR or imatinib effectively inhibited the growth of GIST882 cells in concentration- and time-dependent manner.The inhibitory rate of combined treatment using 5-aza-CdR and imatinib was significantly higher than that of 5-aza-CdR or imatinib alone (P＜0.05).After treatment for 48 h,the apoptosis rates of 5-aza-CdR group (1000 μg/L) and imatinib group (100 μmol/L) were (11.7±1.2)％ and (14.6±0.8)％,respectively.Compared with the control group (2.8±0.3)％,the difference was statistically significant (P=0.000).Furthermore,the difference in apoptosis rate was significant between combined treatment group (19.4±1.1)％ and single drug treatment group (vs.5-aza-CdR group,P=0.000,vs.imatinib group,P=0.013).5-aza-CdR raised G0/G1 ratio and reduced S ratio of GIST882.Imatnib and combined group had no apparent influence on the cell cycle of GIST882 cells.Conclusion 5-aza-CdR may be a potential agent of GIST treatment in the near future.