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H1/pAIM2 纳米颗粒发挥抗肿瘤作用，其与肾癌中的炎性体激活有关。

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

机构信息

Cancer Institute, Xuzhou Medical University, Xuzhou, China.

Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, China.

出版信息

J Cell Mol Med. 2018 Nov;22(11):5670-5681. doi: 10.1111/jcmm.13842. Epub 2018 Aug 30.

DOI:10.1111/jcmm.13842
PMID:30160343
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6201339/
Abstract

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.

摘要

肾细胞癌（RCC）是一种高转移肿瘤，目前治疗方法效果不佳。黑色素瘤缺失因子 2（AIM2）作为一种肿瘤抑制因子，可能成为治疗 RCC 的潜在治疗靶点。在这里，我们发现 AIM2 的表达在 RCC 患者标本和肾癌细胞系（786-O 和 OSRC-2）中明显降低。为了建立安全有效的 AIM2 基因传递系统，我们形成了由叶酸接枝的 PEI600-CyD（H1）纳米颗粒组成的纳米颗粒，将 AIM2 基因（H1/pAIM2）作为有效的递送剂。在肾癌细胞中递送 H1/pAIM2 可以显著增加 AIM2 的表达，随后减少细胞增殖、迁移和侵袭，并增强细胞凋亡。为了评估 AIM2 在体内的治疗效果，我们将 H1/pAIM2 纳米颗粒瘤内注射到 786-O-异种移植小鼠中。H1/pAIM2 纳米颗粒的给药可以抑制肿瘤生长，表现为肿瘤体积和重量的减少。此外，使用炎症小体抑制剂 YVAD-CMK 阻断 H1/pAIM2 纳米颗粒引发的炎症小体激活，消除了 H1/AIM2 的抗肿瘤活性。这些结果表明，H1/pAIM2 纳米颗粒的治疗效果主要归因于其增强炎症小体激活的能力。H1/AIM2 纳米颗粒可能成为治疗 RCC 的有效治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/9fcad2b19cfe/JCMM-22-5670-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/72196ddff915/JCMM-22-5670-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/35889ff21652/JCMM-22-5670-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/c360a738f102/JCMM-22-5670-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/8d4729d48f6b/JCMM-22-5670-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/7cbe6c74be57/JCMM-22-5670-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/e574af50ecff/JCMM-22-5670-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/9fcad2b19cfe/JCMM-22-5670-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/72196ddff915/JCMM-22-5670-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/35889ff21652/JCMM-22-5670-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/c360a738f102/JCMM-22-5670-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/8d4729d48f6b/JCMM-22-5670-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/7cbe6c74be57/JCMM-22-5670-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/e574af50ecff/JCMM-22-5670-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2808/6201339/9fcad2b19cfe/JCMM-22-5670-g007.jpg

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