三氧化二砷诱导胃癌细胞凋亡及对相关基因表达的影响  

EFFECT OF ARSENIC TRIOXIDE ON APOPTOSIS AND APOPTOSIS RELATED GENES IN GASTRIC CANCER CELLS

作　　者：涂水平[1] 江石湖[1] 谭继宏[1] 乔敏敏[1] 王立夫[1] 蒋晓华[1] 吴云林[1] 

机构地区：[1]上海第二医科大学瑞金医院消化科,上海200025

出　　处：《肿瘤》2001年第5期327-330,共4页Tumor

基　　金：上海市科学和技术发展基金资助 ( 96 41190 35 )

摘　　要：目的　研究三氧化二砷 (As2 O3)诱导胃癌细胞的凋亡作用及对凋亡相关基因p5 3、c myc、bcl 2、bcl xl和bcl xs表达的影响 ,探讨其诱导胃癌凋亡的作用机制。方法　研究As2 O3 对胃癌细胞SGC 790 1和MKN 45的诱导凋亡作用和对凋亡相关基因表达的影响。结果　As2 O3 作用于细胞可见典型的细胞凋亡。出现典型的亚二倍体“凋亡峰”。 10 μmol/LAs2 O3 的诱导胃癌细胞SGC 790 1和MKN 45的凋亡率为13 8%和 2 2 5 %。细胞凋亡指数在 1 42 %～ 9 5 %之间。As2 O3 作用后能明显下调SGC 790 1细胞的bcl 2蛋白和mRNA的表达 ;对SGC 790 1细胞的p5 3、c myc、bcl xl和bcl xs蛋白的表达无影响。As2 O3 能促进MKN 45细胞的p5 3蛋白和mRNA的表达 ,对MKN 45细胞的bcl 2、c myc、bcl xl和bcl xs基因表达无影响。结论　As2 O3 可能通过不同途径诱导胃癌细胞凋亡 ,通过下调SGC 790 1细胞的bcl 2的蛋白表达诱导其凋亡 ,通过上调p5 3表达诱导胃癌MKN 45细胞凋亡。Objective To study the mechanisms of arsenic trioxide (As 2O 3) induced apoptosis of gastric cancer cells by detecting expression of gene p53?c myc?bcl 2?bcl xl and bcl xs in gastric cancer cells.Methods Apoptosis of gastric cancer cells (SGC 7901,MKN 45)was measured by TUNEL and flow cytometry. The levels of mRNA and protein of genes p53?c myc?bcl 2?bcl xl and bcl xs were determined by reverse transcription polymerase chain reaciton analysis and immunohistochemistry respectively. Results Gastric cancer cells SGC 7901 and MKN 45 present some typical morphologic features of apoptosis, including nuclear shrinkage chromatin condensation.DNA fragmentation, and formation of apoptotic bodies. After 12 hours exposure to As 2O 3 some typical subdiploid peaks before G0/G1 phase werre observed. The apoptotic rates of SGC 7901, and MKN 45 were 13.8% and 22.5% respectively. The levels of bcl 2 mRNA and protein in SGC 7901 cells were down regulated after treated with As 2O 3. The expression of p53?c myc?bcl xl and bcl xs genes were not affected by As 2O 3 treatment. The levels of p53 mRNA and protein in MKN 45 cells increased after exposure with As 2O 3. The protein expressions of bcl 2?c myc?bcl xl and bcl xs were unchanged in MKN 45 treated with As 2O 3. Conclusion The results showed that As 2O 3 induces apoptosis in gastric cancer cells by regulating the expression of different apoptosis related genes.$$$$

关 键 词：胃癌细胞 三氧化二砷 细胞凋亡 凋亡相关基因 胃癌 治疗实验研究 

分 类 号：R735.2[医药卫生—肿瘤] R730.53[医药卫生—临床医学]