Open AccessH1/ pAIM 2 nanoparticles exert anti‐tumour effects that is associated with the inflammasome activation in renal carcinoma
Author(s) -
Chai Dafei,
Liu Nianli,
Li Huizhong,
Wang Gang,
Song Jingyuan,
Fang Lin,
Lu Zheng,
Yao Hong,
Zheng Junnian
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13842
Subject(s) - inflammasome , renal cell carcinoma , cancer research , apoptosis , in vivo , chemistry , metastasis , cell growth , medicine , cancer , biology , immunology , inflammation , pathology , biochemistry , microbiology and biotechnology
Abstract Renal cell carcinoma ( RCC ) is a high metastasis tumour with less effective treatment available currently. Absent in melanoma 2 ( AIM 2) as a tumour suppressor might be used as a potential therapeutic target for RCC treatment. Here, we found that AIM 2 expression was significantly decreased in RCC patient specimens and renal carcinoma cell lines (786‐O and OSRC ‐2). To establish a safe and effective AIM 2 gene delivery system, we formed the nanoparticles consisting of a folate grafted PEI 600‐CyD (H1) nanoparticle‐mediated AIM 2 gene (H1/ pAIM 2) as an effective delivery agent. Delivery of H1/ pAIM 2 in renal carcinoma cells could remarkably increase the expression of AIM 2, and subsequently decrease cell proliferation, migration, and invasion as well as enhance cell apoptosis. In order to evaluate the therapeutic efficacy of AIM 2 in vivo, H1/ pAIM 2 nanoparticles were injected intratumorally into 786‐O‐xenograft mice. Administration of H1/ pAIM 2 nanoparticles could inhibit the tumour growth as evidenced by reduced tumour volume and weight. Furthermore, Blockade of inflammasome activation triggered by H1/ pAIM 2 nanoparticles using inflammasome inhibitor YVAD‐ CMK abrogated the anti‐tumoral activities of H1/ AIM 2. These results indicated the therapeutic effect of H1/ pAIM 2 nanoparticles was mainly attributable to its capability to enhance the inflammasome activation. H1/ AIM 2 nanoparticles might act as an efficient therapeutic approach for RCC treatment.