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探讨抗基因及反义寡核苷酸对肝癌的潜在治疗作用。方法合成了针对Ｎ－ｒａｓ转录、翻译起始区的１２ｍｅｒ硫代磷酸抗基因寡脱氧核苷酸（Ｓ－ＯＤＨａｎ）、１９ｍｅｒ硫代磷酸反义寡脱氧核苷酸（Ｓ－ＯＤＮＡａｓ）。采用ＥＬＩＳＡ、斑点杂交法分别检测了寡脱氧核苷酸处理的肝癌ＢＥＬ７４０２细胞内ｐ２１、Ｎ－ｒａｓｍＲＮＡ水平，观察了对ＢＥＬ７４０２肝癌细胞生长的影响。结果处理细胞内Ｎ－ｒａｓｍＲＮＡ水平低于对照组，以Ｓ－ＯＤＮａｎ组更明显。两者对ｐ２１合成的抑制率达８０％，６７．５％。两者的细胞生长抑制率达８８％、７７％，并呈剂量依赖性。两者处理的细胞３Ｈ－ＴｄＲ掺入降低为对照组的２１．８％、３０．５５％；ＡＦＰ水平明显低于对照组（Ｐ直＜０．００１）。结论Ｓ－ＯＤＮａｎ．Ｓ－ＤＤＮａｓ能有效抑制Ｎ－ｒａｓ表达及相关肝癌细胞增殖；也进一步说明Ｎ－ｒａｓ在肝癌发生中起作重要作用。
To explore the potential therapeutic effects of anti-gene and antisense oligonucleotides on liver cancer. Methods A 12mer phosphorothioate anti-nucleotide oligodeoxynucleotide (S-ODHan) and a 19mer phosphorothioate antisense oligodeoxynucleotide (S-ODNAas) were synthesized for N-ras transcription and translation initiation region. The levels of p21 and N-ras mRNA in BEL7402 cells treated with oligodeoxynucleotides were detected by ELISA and dot blot hybridization, respectively, and the effects on the growth of BEL7402 hepatoma cells were observed. Results The level of N-ras mRNA in the treated cells was lower than that in the control group, which was more pronounced in the S-ODNan group. The inhibition rate of p21 synthesis was 80% and 67.5%. The cell growth inhibition rate of both was 88% and 77%, and it was dose-dependent. The 3H-TdR incorporation of both cells was reduced to 21.8% and 30.55% in the control group; the AFP level was significantly lower than that in the control group (P<0.001). Conclusion S-ODNan. S-DDNas can effectively inhibit the expression of N-ras and the proliferation of related hepatocellular carcinoma cells. It also further demonstrates that N-ras plays an important role in the occurrence of hepatocellular carcinoma.