H1/pAIM2 nanoparticles exert anti-tumour effects that is associated with the inflammasome activation in renal carcinoma.

H1/pAIM2 nanoparticles exert anti-tumour effects that is associated with the inflammasome activation in renal carcinoma.
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H1/pAIM2 纳米颗粒发挥与肾癌炎症小体激活相关的抗肿瘤作用

DOI:
10.1111/jcmm.13842
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发表时间:
2018-11
影响因子:
5.3
通讯作者:
Zheng J
Zheng J
中科院分区:
医学2区
文献类型:
--
作者:
Chai D;Liu N;Li H;Wang G;Song J;Fang L;Lu Z;Yao H;Zheng J

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肾细胞癌(Renal cell carcinoma,RCC)是一种高转移性肿瘤,目前治疗效果较差.作为肿瘤抑制因子的AIM 2可能被用作RCC治疗的潜在治疗靶点。在这里,我们发现RCC患者标本和肾癌细胞系(786-O和OSRC-2)中AIM 2表达显着降低。为了建立安全有效的AIM 2基因递送系统,我们形成了由叶酸接枝的PEI 600-CyD(H1)纳米颗粒介导的AIM 2基因(H1/pAIM 2)组成的纳米颗粒作为有效的递送剂。H1/pAIM 2转染肾癌细胞后,AIM 2的表达明显增加,细胞增殖、迁移、侵袭能力下降,细胞凋亡增加。为了评估AIM 2在体内的治疗功效,将H1/pAIM 2纳米颗粒瘤内注射到786-O-异种移植小鼠中。施用H1/pAIM 2纳米颗粒可以抑制肿瘤生长,如通过减少的肿瘤体积和重量所证明的。此外,使用炎性小体抑制剂YVAD-CMK阻断由H1/pAIM 2纳米颗粒触发的炎性小体激活消除了H1/AIM 2的抗肿瘤活性。这些结果表明,H1/pAIM 2纳米粒的治疗效果主要归因于其增强炎性小体活化的能力。H1/AIM 2纳米粒有望成为治疗肾细胞癌的有效方法。
Renal cell carcinoma (RCC) is a high metastasis tumour with less effective treatment available currently. Absent in melanoma 2 (AIM2) as a tumour suppressor might be used as a potential therapeutic target for RCC treatment. Here, we found that AIM2 expression was significantly decreased in RCC patient specimens and renal carcinoma cell lines (786‐O and OSRC‐2). To establish a safe and effective AIM2 gene delivery system, we formed the nanoparticles consisting of a folate grafted PEI600‐CyD (H1) nanoparticle‐mediated AIM2 gene (H1/pAIM2) as an effective delivery agent. Delivery of H1/pAIM2 in renal carcinoma cells could remarkably increase the expression of AIM2, and subsequently decrease cell proliferation, migration, and invasion as well as enhance cell apoptosis. In order to evaluate the therapeutic efficacy of AIM2 in vivo, H1/pAIM2 nanoparticles were injected intratumorally into 786‐O‐xenograft mice. Administration of H1/pAIM2 nanoparticles could inhibit the tumour growth as evidenced by reduced tumour volume and weight. Furthermore, Blockade of inflammasome activation triggered by H1/pAIM2 nanoparticles using inflammasome inhibitor YVAD‐CMK abrogated the anti‐tumoral activities of H1/AIM2. These results indicated the therapeutic effect of H1/pAIM2 nanoparticles was mainly attributable to its capability to enhance the inflammasome activation. H1/AIM2 nanoparticles might act as an efficient therapeutic approach for RCC treatment.
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发表时间: 2015
影响因子: --
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发表时间: 2013
期刊: PloS one
影响因子: 3.7
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