全反式维甲酸、三氧化二砷联合地西他滨对SK-N-SH细胞系活性及分化的影响  

The combination of DAC can improve the cytotoxicity and differentiation of ATRA and ATO of neuroblastoma SK-N-SH cell line

作　　者：黎阳[1] 刘利婷 冯楚础 熊稀霖[1] 彭晓敏[1] 邬萍萍 翁文骏[1] LI Yang;LIU Liting;FENG Chuchu;XIONG Xilin;PENG Xiaomin;WU Pingping;WENG Wenjun(Pediatric Oncology Department,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China;Pediatric Hematology/Oncology Department,Third Affiliated Hospital,Sun Yat-Sen University,Guangzhou 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院儿科肿瘤专科,广州510120 [2]中山大学附属第三医院儿科血液/肿瘤专科,广州510530

出　　处：《中国小儿血液与肿瘤杂志》2019年第5期234-240,共7页Journal of China Pediatric Blood and Cancer

基　　金：广东省自然科学基金资助(2017A030313806)

摘　　要：目的通过检测全反式维甲酸(ATRA)、三氧化二砷(ATO)联合地西他滨(DAC)对神经母细胞瘤(NB)细胞系SK-N-SH活性及分化的影响,探讨上述药物联合应用提高NB疗效的可能性。方法不同浓度ATRA和DAC处理SK-N-SH细胞,测定其IC50。测定单药或联合用药处理后细胞的凋亡率并记录细胞形态;采用SPSS 20.0分析数据。结果(1)ATRA及DAC均可抑制NB细胞增殖、促进凋亡,IC50(ATRA)=372.5μM,IC50(DAC)=452.5μM。(2)10μM ATRA联合DAC处理NB细胞,其凋亡率为(7.31±0.94)%,高于ATRA单药组(4.90±1.58)%和DAC单药组(4.62±0.99)%。3μM ATO联合DAC处理细胞,其凋亡率由(8.44±0.86)%增加至(15.51±1.80)%。(3)1μM、10μM浓度ATRA处理SK-N-SH细胞,开始分化的时间分别为7天和3天;随时间延长,细胞分化、死亡增多。5μM DAC单药,持续观察9天,未见分化细胞。联合用药组细胞分化出现更早。结论(1)ATRA、DAC对SK-N-SH细胞有抑制增殖、促进凋亡和诱导分化的作用;(2)联合去甲基化药物DAC可提高ATRA对SK-N-SH细胞的杀伤作用和诱导分化作用;(3)联合去甲基化药物DAC可提高ATO对SK-N-SH细胞的杀伤作用。Objective To detect the effects of all-trans retinoic acid(ATRA)and arsenic trioxide combined with decitabine(DAC)on viability and differentiation of Neuroblastoma SK-N-SH Cell Line,and to explore the possibility of demethylating drugs in combination with chemotherapy as a therapeutic agent in the treatment of NB.Methods Different concentrations of decitabine and all-trans retinoic acid were added to measure IC50,and then apoptosis index and morphologic changes of NB cells were investigated.Data processing was based on SPSS 20.0 statistical software.Results(1)ATRA and DAC inhibits proliferation,and promotes apoptosis of SK-N-SH cells.The IC50(ATRA)equals to 372.5μM,while the IC50(DAC)equals to 452.5μM.(2)The apoptosis rate for 10μM ATRA was(4.90±1.58)%,while the apoptosis rate was(7.31±0.94)%after treatment of low-dose DAC.There was a significant difference between the DAC group and the combination group.The apoptosis rate for 3μM arsenic trioxide for 48 hours was(8.44±0.86)%,while 5μM DAC treated for 24h firstly the apoptosis rate increased to(15.51±1.80)%.(3)After treated with 1μM or 10μM ATRA,SK-N-SH cells began to differentiate in 7 days and 3 days,respectively,and with the prolonged duration,there was more cell differentiations and deaths.There was no cell differentiation after continuous treatment with 5μM DAC for 9 days.Cell differentiation appeared earlier in the combined drug group.Conclusions(1)ATRA and DAC inhibits proliferation,promotes apoptosis and induces differentiation of SK-N-SH cells.(2)The combination of DAC can enhance the cytotoxicity and differentiation of ATRA in vitro.(3)The combination of DAC can improve the cytotoxicity of ATO in vitro.

关 键 词：神经母细胞瘤 全反式维甲酸 三氧化二砷 地西他滨 甲基化 

分 类 号：R73[医药卫生—肿瘤]