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Gene therapy in a mouse tumor model of breastcancer by siRNA-mediated down-regulation of STAT3

机译:siRNA介导的STAT3下调在乳腺癌小鼠模型中的基因治疗

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Breast carcinoma is one of the most common forms of cancer, with a high prevalence and mortality rate worldwide. Signal transducer and activator of transcription 3 (STAT3) plays a key role in tumor cell survival and proliferation, angiogenesis, apoptosis. It is aberrantly activated in several types of cancers, including breast cancer. We assessed the therapeutic effects using a DNA vector-based STAT3-specific small interfering RNA (pSi-STAT3) on a murine breast cancer model. We observed the tumor growth in evry groups and further discussed the mechanism underlying. STAT3 was significantly down- regulated at both the mRNA and protein levels in the pSi-STAT3 group. The growth of the tumors was significantly reduced in the pSi-STAT3-treated mice. Flow cytometry revealed that the number of early apoptotic cells was significantly elevated in the pSi-STAT3 group. Moreover, in the pSi-STAT3 group, the mRNA expression of the STAT3 downstream genes Bcl2 and c- Myc was also significantly inhibited, and immunohistochemistry revealed that the expression of STAT3, HIF1 and PCNA protein were reduced in the tumor tissues. Our results suggested that STAT3-specific siRNA significantly suppressed tumor growth in breast cancer-bearing mice. It might be a useful therapeutic strategy in malignancies.
机译:乳腺癌是最常见的癌症形式之一,在世界范围内患病率和死亡率很高。信号转导和转录激活因子3(STAT3)在肿瘤细胞的存活和增殖,血管生成,细胞凋亡中起着关键作用。它在包括乳腺癌在内的多种类型的癌症中异常激活。我们使用基于DNA载体的STAT3特异性小干扰RNA(pSi-STAT3)对小鼠乳腺癌模型评估了治疗效果。我们观察了各组肿瘤的生长,并进一步讨论了潜在的机制。 STAT3在pSi-STAT3组的mRNA和蛋白水平均显着下调。在pSi-STAT3处理的小鼠中,肿瘤的生长明显减少。流式细胞仪显示,pSi-STAT3组的早期凋亡细胞数量明显增加。此外,在pSi-STAT3组中,STAT3下游基因Bcl2和c-Myc的mRNA表达也被显着抑制,并且免疫组织化学显示在肿瘤组织中STAT3,HIF1和PCNA蛋白的表达降低。我们的研究结果表明,STAT3特异性siRNA可以显着抑制荷瘤小鼠的肿瘤生长。它可能是恶性肿瘤的有用治疗策略。

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