β1整合素反义寡核苷酸对人胰腺癌细胞BXPC-3生长和化疗敏感性的影响

The Effect of Integrin-β1 Antisense Oligodexynucleotides on Cell Growth and Chemosensitivity of Pancreatic Cancinoma Cell BXPC-3

    摘要
  • 摘要: 目的:观察β1整合素反义寡核苷酸(ASODNs)对人胰腺癌细胞BXPC-3β1整合素mRNA表达及细胞生长和对化疗药物敏感性的影响。方法:采用脂质体将不同浓度β1整合素ASODNs转染到人胰腺癌细胞BXPC-3中,逆转录-聚合酶链反应(RT-PCR)检测细胞β1整合素mRNA表达水平,MTT法检测细胞相对存活率。转染β1整合素ASODNs24h后,给予梯度浓度5-氟尿嘧啶(5-FU)、阿霉素和健择,观察量效关系,计算IC50。结果:与对照组相比,32mg/L～128mg/LASODNs转染后可抑制胰腺癌细胞的生长,且呈量效依赖关系,64mg/L和128mg/L抑制作用最明显,其对应的β1整合素mRNA表达水平显著降低。转染β1整合素ASODNs能增加胰腺癌细胞对化疗药物的敏感性,ASODNs+化疗组对各化疗药物的IC50均有显著下降。结论:靶向β1整合素的反义寡核苷酸可有效阻断其在人胰腺癌细胞中的表达,抑制胰腺癌细胞生长,增强对化疗药物敏感性。

     

    Abstract: Objective :To investigate the effects of integrin-β1 antisense oligodexynucleotides(ASODNs)on cell-growth and chemosensitivity of pancreatic cancinoma cell line BXPC-3. Methods :Integrin-β1 antisense oligodexynucleotides was transfected into BXPC-3 with liposome.The expression of integrin-β1 mRNA was determined by RT-PCR.The viability rate was assessed by MTT method.Different concentrations of 5-FU,adriamycin(ADM),Gemcitabine were given 24 h after cells transfected with integrin-β1 ASODNs.The dose-effects responses were observed and IC50 s were calculated. Results :Transfecting BXPC-3 cells with 32mg/L～128mg/L integrin-β1 ASODNs inhibited growth significantly and reduced expression of integrin-β1 mRNA.Integrin-β1 ASODNs increased the chemosensitivity of BXPC-3 cells to 5-FU,ADM,Gemcitabine.The IC50 s of different chemotherapy groups were significantly lower than those in controls. Conclusion :Integrin-β1 ASODNs can effectively decrease the expression of integrin-β1 gene,inhibits cell growth and enhances the chemosensitivity in pancreatic cancinoma cell line BXPC-3.

     

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