title: Heat shock protein inhibitor, quercetin, as a novel adjuvant agent to improve radiofrequency ablation-induced tumor destruction and its molecular mechanism.
abstract: BACKGROUND
  We investigated the effect of a small molecular inhibitor of heat shock protein (HSP), quercetin, on tumor radiofrequency (RF) ablation, and explored the underlying molecular mechanisms.
  
  
  METHODS
  In in vivo study, rats with R3230 breast adenocarcinoma were sacrificed 24 h post-treatment and gross coagulation areas were compared, and next, randomized into four treatment arms (control, quercetin alone, RF alone, and combination) for Kaplan-Meier analysis of defined endpoint survival. Then the distribution and expression levels of heat shock protein 70 (HSP70), cleaved caspase-3 and heat shock factor 1 (HSF1) were analyzed after different treatments. In in vitro study, we used quercetin to promote SK-HEP-1 (hepatic) and MCF-7 (breast) cancer cell apoptosis in heat shock cell model, and siRNA was used to block c-Jun and to explore the role of activating protein-1 (AP-1) signaling pathways.
  
  
  RESULTS
  We found the effects of quercetin plus RFA resulted in increase on the tumor destruction/endpoint survival (26.5±3.4 d) in vivo, compared with RF alone (17.6±2.5 d) and quercetin alone (15.7±3.1 d). Most importantly, quercetin-induced cancer cell death required the presence of HSF1 in animal model. Furthermore, quercetin directly down-regulated expression of HSF1 in vitro, which our findings have revealed, required the activation of AP-1 signaling pathways by loss-of-function analysis using siRNA mediated targeting of c-Jun.
  
  
  CONCLUSIONS
  These results indicated a protective role of quercetin in tumor ablation and highlighted a novel mechanism involving HSP70 with HSF1 pathway in thermal ablation of solid tumors.
authors.affiliation: 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China ; 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China ; 4 Department of Cardiovascular and Neurovascular, Guangzhou Medical University, Guangzhou 510182, China ; 5 Department of Oncology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China ; 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China ; 4 Department of Cardiovascular and Neurovascular, Guangzhou Medical University, Guangzhou 510182, China ; 5 Department of Oncology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cui
authors.affiliation: 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China ; 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China ; 4 Department of Cardiovascular and Neurovascular, Guangzhou Medical University, Guangzhou 510182, China ; 5 Department of Oncology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Jungchieh
authors.initials: J
authors.lastname: Lee
authors.affiliation: 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China ; 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China ; 4 Department of Cardiovascular and Neurovascular, Guangzhou Medical University, Guangzhou 510182, China ; 5 Department of Oncology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China ; 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China ; 4 Department of Cardiovascular and Neurovascular, Guangzhou Medical University, Guangzhou 510182, China ; 5 Department of Oncology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China ; 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China ; 4 Department of Cardiovascular and Neurovascular, Guangzhou Medical University, Guangzhou 510182, China ; 5 Department of Oncology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fu
authors.affiliation: 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China ; 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China ; 4 Department of Cardiovascular and Neurovascular, Guangzhou Medical University, Guangzhou 510182, China ; 5 Department of Oncology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Gongxiong
authors.initials: G
authors.lastname: Wu
authors.affiliation: 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing 100142, China ; 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China ; 4 Department of Cardiovascular and Neurovascular, Guangzhou Medical University, Guangzhou 510182, China ; 5 Department of Oncology, The first Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yan
keywords: Radiofrequency ablation (RFA); heat shock protein (HSP); quercetin; solid tumor