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首页> 外文期刊>Tumour biology : >Antisense oligodeoxynucleotide directed against c-myb has anticancer activity and potentiates the antiproliferative effect of conventional anticancer drugs acting by different mechanisms in human colorectal cancer cells.
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Antisense oligodeoxynucleotide directed against c-myb has anticancer activity and potentiates the antiproliferative effect of conventional anticancer drugs acting by different mechanisms in human colorectal cancer cells.

机译:针对c-myb的反义寡聚脱氧核苷酸具有抗癌活性,并增强了常规抗癌药物通过不同机制作用于人结直肠癌细胞的抗增殖作用。

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摘要

The C-MYB proto-oncogene encodes a DNA-binding protein with transactivation properties that plays an important regulatory role in cell proliferation and differentiation. Overexpression of C-MYB in colonic tumors compared to normal mucosa suggests that c-myb may play a role in the malignant transformation of colonic mucosa and that inhibition of c-myb expression may suppress, to some extent, the proliferation of neoplastic cells. Complete suppression of tumor cell proliferation may require inhibition of multiple growth-promoting genes. Alternatively, the combination of oncogene-targeted oligodeoxynucleotides (ODNs) with standard cytotoxic agents might represent a useful therapeutic approach to improving cancer treatment. In the present study, we have investigated whether the inhibition of a growth-promoting gene, namely c-myb, affects the sensitivity of human colorectal cancer cells, in vitro, to conventional chemotherapeutic drugs: taxol, 5-fluorouracil, vinblastine and doxorubicin. We show that c-myb antisense phosphorothioate (S) ODN treatment induces growth arrest in the G(1)/G(2) phases of the cell cycle and inhibits cell proliferation in a dose- and time-dependent manner. Also, treatment with c-myb antisense (S)ODN decreases c-myb mRNA and protein expression. A greater inhibition of cell proliferation in vitro was obtained with the combination of c-myb (S)ODN and cytotoxic drugs. The combinations exerted additive and synergistic effects on human colorectal cancer cells. This study suggests that c-myb antisense (S)ODN might be useful in the therapy of colorectal cancer in combination with chemotherapeutic drugs.
机译:C-MYB原癌基因编码具有反式激活特性的DNA结合蛋白,该蛋白在细胞增殖和分化中起重要的调节作用。与正常粘膜相比,C-MYB在结肠肿瘤中的过度表达表明c-myb可能在结肠粘膜的恶性转化中起作用,并且抑制c-myb的表达可以在一定程度上抑制肿瘤细胞的增殖。完全抑制肿瘤细胞增殖可能需要抑制多个促进生长的基因。或者,靶向癌基因的寡脱氧核苷酸(ODN)与标准细胞毒剂的组合可能代表改善癌症治疗的有用治疗方法。在本研究中,我们研究了抑制生长促进基因c-myb在体外是否会影响人类结直肠癌细胞对常规化疗药物:紫杉醇,5-氟尿嘧啶,长春碱和阿霉素的敏感性。我们显示c-myb反义硫代磷酸酯(S)ODN处理诱导细胞周期的G(1)/ G(2)阶段的生长停滞,并以剂量​​和时间依赖性的方式抑制细胞增殖。同样,用c-myb反义(S)ODN处理可降低c-myb mRNA和蛋白质表达。 c-myb(S)ODN和细胞毒性药物的组合在体外获得了更大的细胞增殖抑制作用。该组合对人结肠直肠癌细胞发挥累加和协同作用。这项研究表明c-myb反义(S)ODN可能与化学治疗药物联合用于治疗大肠癌。

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