摘要
目的 了解三螺旋形成寡核苷酸（ＴＦＯ）、反义寡核苷酸（ＯＤＮａｓ）抑制肝癌细胞生长的作用。方法 以Ｎ－ｒａｓ第二转录起始位点及翻译起始区１－６密码为靶点，合成１２聚硫代磷酸ＴＦＯ（ＴＦＯ１２）、１９聚硫代磷酸ＯＤＮａｓ（ＯＤＮａｓ１９）、同时合成１９聚无关序列硫代磷酸寡核苷酸对照（ＯＤＮｃｏｎ）。在人肝癌Ｂｅｌ７４０２细胞观察了充代磷酸寡核苷酸对Ｎ－ｒａｓ表达ｐ２１蛋白的抑制及对细胞增殖的影响。
Objective: To evaluate effect of triplex forming oligodeoxynucleotides (TFO) and antisense oligodeoxynucleotides (ODNas) on proliferation of human hepatocellular carcinoma cells. Methods: A 12 mer phosphorothioate TFO (TFO12) directed at the second transcriotion start site of N-ras gene and a 19 mer phosphorothioate ODNas (ODNas19) complementary to translation initiation codon and downstream 5 codons of N-ras mRNA were synthesized. A 19 mer unrelated phosphorothioate TFO(ODNcon) was olso synthesized and used as control effect of TFO12 and ODNas19 on synthesis of p21 and proliferation of human hepatocellular carcinoma Bel 7402 cells were examined. Results: TFO12 and ODNas19 reduced synthesis of p21 by 80. 2% and 67. 5%, respectively. At concentration of 16μmol/L, TFO12 and ODNas21 inhibited proliferation of Bel 7402 cells by 88% and 77%, respectively. In the Bel 7402 cells treated with TFO12 and ODNas19, ~3H-thymidine incorporation was decreased 78. 2% and 69.5% respectively. The growth inhibitions of TFO12 and ODNas19 were dose-dependent, and were observed at 6 hour after administration, reached the highest point at 12 hour. The mixture of TFO12 and ODNas19 was more effective than TFO12 or ODNas19 alone. No inhibitions were observed in ODNcon group. Conclusion: Triplex forming oligodeoxynucleotides and antisense oligodeoxynucleotides were both potential inhibitor for expression of N-ras and proliferation of hepatocellular carcinoma cells.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2000年第6期527-529,共3页
Chinese Journal of Cancer
关键词
肝肿瘤
N-ras癌基因
反义寡脱氧核苷酸
TFO
Liver neoplasms
N-ras oncogene
Triplex forming oligodeoxynucleotides
Antisense oligodeoxynucleotides
