地西他滨联合三氧化二砷对肝癌SMMC-7721细胞株P15^(INK4B)及甲基化转移酶表达的影响  

Decitabine Combined with Arsenic Trioxide Effects the Expression of P15^(INK4B) and DNA Methyltrans-ferase in Liver Cancer SMMC-7721 Cell Line

作　　者：边祥海[1] 孙贵富[1] BIAN Xianghai;SUN Guifu(Department of Oncology,Zhejiang Haiyan People＇s Hospital,Haiyan（314300）,China)

机构地区：[1]浙江省海盐县人民医院肿瘤内科,海盐314300

出　　处：《浙江中西医结合杂志》2018年第11期924-927,共4页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：浙江省嘉兴市海盐县科技局计划项目(No.2016Y3B2012)

摘　　要：目的探讨地西他滨(DAC)和三氧化二砷(As_2O_3)对肝癌SMMC-7721细胞株P15^(INK4B)抑癌基因及甲基化转移酶表达的影响。方法 MTT方法检测地西他滨和三氧化二砷对SMMC-7721细胞株的抑制率。RT-PCR方法检测P15^(INK4B)、DNA甲基转移酶1(DNMT1)、DNMT3A、DNMT3B mRNA的表达。结果 2.0mmol/LDAC和2.0μmol/L As_2O_3联用,肝癌SMMC-7721细胞株细胞增殖抑制率均较4.0mmol/LDAC、4.0μmol/L As_2O_3单药组增强[(72h:(69.9±1.2)%比(33.8±0.7)%、(47.9±2.5)%,P<0.05)]。地西他滨和As_2O_3作用细胞72h后P15^(INK4B)抑癌基因表达增强,联合组同4.0mmol/LDAC、4.0μmol/L As_2O_3单药组比较,差异有统计学意义[(0.74±0.14)比(0.57±0.15)、(0.56±0.11),P<0.05];甲基化转移酶表达水平下调,联合组同4.0mmol/LDAC、4.0μmol/L As_2O_3单药组比较,差异有统计学意义[DNMT3A:(0.28±0.11)比(0.36±0.13)、(0.41±0.13),P<0.05;DNMT3B:(0.32±0.13)比(0.39±0.12)、(0.45±0.16),P<0.05;DNMT1:(0.31±0.15)比(0.44±0.19)、(0.44±0.12),P<0.05]。结论地西他滨和三氧化二砷可能通过抑制肝癌SMMC-7721细胞株甲基化转移酶,增加P15^(INK4B)基因表达来抑制肝癌细胞增殖。Objective To investigate the effects of decitabine（DAC）combined with arsenic trioxide（As2O3）onthe expression of P15INK4B tumor suppressor gene and DNA methyltransferase in hepatocellular carcinoma SMMC-7721 cell lines. Methods MTT method was used to observe the suppression ratio of drugs on the proliferation ofSMMC-7721 cells. RT-PCR was performed to detect mRNA expression of P15INK4B, and DNA methyltransferases（DNMTs）, i.e., DNMT1, DNMT3A and DNMT3B. Results After 72h treating with 2.0mmol∕L DAC and 2.0μmol∕LAs2O3, the suppression ratio of SMMC-7721 proliferation increased, compare to those of the single drug groups（ei-ther 4.0mmol/L DAC or 4.0μmol∕L As2O3）[（69.9±1.2）% vs（33.80.7）% and（47.92.5）%, P〈0.05]. Also, the expression of P15INK4B increased significantly[（0.74±0.14）vs（0.57±0.15）and（0.56±0.11）, P〈0.05], and the expres-sion of DNMTs decreased significantly, DNMT3：（0.28±0.11）vs（0.36±0.13）and（0.41±0.13）（P〈0.05）; DNMT3B：（0.32±0.13）vs（0.39±0.12）and（0.45±0.16）（P0.05）; DNMT1：（0.31±0.15）vs（0.44±0.19）and（0.44±0.12）（P0.05）. Conclusion Decitabine and arsenic trioxide could inhibit the proliferation of SMMC-7721 liver cancer cellby suppressing methyltransferases and increasing the expression of P15INK4B gene.

关 键 词：肝癌SMMC-7721细胞株 地西他滨 三氧化二砷 P15^INK4B 甲基化转移酶 

分 类 号：R735.7[医药卫生—肿瘤]