TY - JOUR AU - Yang, Wei AU - Cui, Ming AU - Lee, Jungchieh AU - Gong, Wei AU - Wang, Song AU - Fu, Jingjing AU - Wu, Gongxiong AU - Yan, Kun PY - 2016 TI - Heat shock protein inhibitor, quercetin, as a novel adjuvant agent to improve radiofrequency ablation-induced tumor destruction and its molecular mechanism JF - Chinese Journal of Cancer Research; Vol 28, No 1 (February 29, 2016): Chinese Journal of Cancer Research Y2 - 2016 KW - N2 - 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. UR - https://cjcr.amegroups.org/article/view/9350