Open AccessAbsent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer
Author(s) -
Chai Dafei,
Qiu Dong,
Zhang Zichun,
Yuchen Shi Shang,
Wang Gang,
Fang Lin,
Li Huizhong,
Li Hailong,
Tian Hui,
Zheng Junnian
Publication year - 2020
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.15697
Subject(s) - cancer research , oncolytic virus , aim2 , promoter , biology , oncolytic adenovirus , cancer cell , cancer , inflammasome , immunology , inflammation , biochemistry , gene expression , tumor cells , gene , genetics
Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX promotor )‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX promotor ‐AIM2 adenoviruses (Ad‐CAIX promotor ‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIX promotor , Ad‐CAIX promotor ‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIX promotor ‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIX promotor ‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIX promotor ‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIX promotor ‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.