OncoTargets and Therapy (Sep 2020)
Curcumin Negatively Regulates Cigarette Smoke-Induced Renal Cell Carcinoma Epithelial–Mesenchymal Transition Through the ERK5/AP-1 Pathway
Abstract
Tao Zhang,1,* Li Zhao,2,* Taotao Zhang,1,* Wangyu Wu,1 Jie Liu,3 Xian Wang,1 Yang Wan,4 Hao Geng,1 Xin Sun,1 Weiwei Qian,1 Dexin Yu1 1Department of Urologic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, People’s Republic of China; 2Department of Urologic Surgery, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, 210048, People’s Republic of China; 3Department of Urologic Surgery, The First People’s Hospital of Wuhu, Wuhu 241000, People’s Republic of China; 4Department of Hematology/Hematological Lab, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dexin YuDepartment of Urologic Surgery, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Road, Hefei 230032, People’s Republic of ChinaEmail [email protected]: So far, little research has been conducted regarding the underlying mechanism of renal carcinogenesis at molecular level. Epithelial–mesenchymal transition (EMT) exerts an important part during tumor genesis as well as the development through mitogen-activated protein kinase (MAPK) pathways. Therefore, we hypothesized that EMT could promote renal cell carcinoma (RCC) progression via the ERK5/AP-1pathway.Materials and Methods: The RCC cell lines were utilized to be the models with in vitro exposure to cigarette smoke extract (CSE). We used the curcumin for the EMT intervention study. In the present study, immunohistochemistry (IHC), Western blotting, and real-time quantitative reverse transcription PCR had been used to determine the experimental results. EMT phenotypic alterations were assessed by changes in cell morphology, invasion and transfer ability, as well as expression of epithelial and mesenchymal markers.Results: In human renal cell carcinoma tissue, E-cadherin expression within the smoking renal cancer patients was down-regulated compared with that among the non-smokers. However, Vimentin, N-cadherin, and TWIST levels increased (P< 0.05). Significantly, we clarified that ERK5/AP-1 exerted positive regulation on the renal cell carcinoma EMT mediated by CS, which was suggested based on the results of CS activating the ERK5/AP-1 pathway, as well as ERK5 inhibition via XMD8-92 reversed AP-1 protein levels and the EMT process. Furthermore, curcumin showed the same inhibitory effect as XMD8-92 and significantly reversed CS-induced EMT through inhibiting the ERK5/AP-1 signaling pathway.Conclusion: The above results indicated that ERK5/AP-1 signaling pathway exerts a vital part for CS-associated RCC development and cancer intervention.Keywords: renal cell carcinoma, epithelial–mesenchymal transition, cigarette smoke, ERK5/AP-1 pathway, curcumin
