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肿瘤细胞p53突变状况对p53基因治疗的影响[J]. 肿瘤防治研究, 2010, 37(03): 301-304. DOI: 10.3971/j.issn.1000-8578.2010.03.016
引用本文: 肿瘤细胞p53突变状况对p53基因治疗的影响[J]. 肿瘤防治研究, 2010, 37(03): 301-304. DOI: 10.3971/j.issn.1000-8578.2010.03.016
Influence of p53 Mutation Status in Tumor Cells to Gene Therapy of Adv-p53[J]. Cancer Research on Prevention and Treatment, 2010, 37(03): 301-304. DOI: 10.3971/j.issn.1000-8578.2010.03.016
Citation: Influence of p53 Mutation Status in Tumor Cells to Gene Therapy of Adv-p53[J]. Cancer Research on Prevention and Treatment, 2010, 37(03): 301-304. DOI: 10.3971/j.issn.1000-8578.2010.03.016

肿瘤细胞p53突变状况对p53基因治疗的影响

Influence of p53 Mutation Status in Tumor Cells to Gene Therapy of Adv-p53

  • 摘要: 目的 探讨肿瘤细胞p53突变状况对p53基因治疗的影响。 方法 PCR-SSCP及DNA测序分析MCA-205和Panc-02细胞的p53基因突变状况;流式细胞计数了解腺病毒载体对这两种细胞的转导情况;TUNEL方法分析转导p53基因后的细胞凋亡情况,培养细胞计数分析对离体肿瘤细胞生长的影响;利用小鼠肝转移肿瘤模型,分析Adv-p53对于在体肿瘤的抗肿瘤作用。 结果 MCA-205细胞p53基因的第769个碱基由G突变为T,Panc-02细胞未发现p53基因突变。腺病毒载体在Panc-02细胞有较高的转导率,而Adv-p53在MCA-205细胞诱导更明显的细胞凋亡。Adv-p53在离体细胞培养试验中抑制MCA-205细胞的生长,而没有明显抑制Panc-02细胞的生长。在小鼠肝转移肿瘤模型中,门静脉注射Adv-p53明显抑制MCA205肝转移肿瘤的生长,而在Panc-02肝转移肿瘤中抗肿瘤作用不明显。 结论 Adv-p53的抗肿瘤作用在有p53基因突变的肿瘤细胞中效果明显,肿瘤细胞p53突变状况对p53基因治疗有一定影响。

     

    Abstract: Objective To investigate the influence of p53 mutation status in tumor cells to the gene therapy of Adv-p53. Methods The mutation status of p53 gene in MCA-205 and Panc-02 cells was analyzed by SSCP -PCR and DNA sequence. The transduction ratio of adenovirus vectors was analyzed by flow cytometric analysis. Apoptosis of tumor cellstransfected with Adv-p53 was analyzed by TUNEL assay. Anti-tumor effect of Adv-p53 was examined in murine liver metastasis model. Results p53 gene in MCA-205 cells had a mutation in 769th base from G to T. p53 gene in Panc-02 cells had not a mutation. The transduction ratio of adenovirus vectors was higher inthat ofPanc-02 cells, but apoptosis after transfected with Adv-p53 was more significant in MCA-205 cells. Invitro experiment, growth of tumor cells was inhibited by Adv-p53 in MCA-205 cells,but not in Panc-02 cells. In murine liver metastasis model, the growth ofMCA-205 tumors was inhibited by intra-portal administration of Adv-p53, but the growth of Panc-02 tumors wasnotinhibited. Conclusion The anti-tumor effect of Adv-p53 was more significant in tumor cells with a mutation of p53 gene. The effect of gene therapy of Adv-p53 was influenced by p53 mutation status in tumor cells

     

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