Cancer Management and Research (May 2020)
Curcumin Affects Gastric Cancer Cell Migration, Invasion and Cytoskeletal Remodeling Through Gli1-β-Catenin
Abstract
Xiao Zhang,1,* Chenli Zhang,1,* Zhiheng Ren,1 Fangfang Zhang,1 Jinyu Xu,1 Xu Zhang,1 Haixue Zheng2 1Department of Pathology, School of Basic Medicine, Lanzhou University, Lanzhou, Gansu 730000, People’s Republic of China; 2National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu ZhangDepartment of Pathology, School of Basic Medicine, Lanzhou University, 222 Tianshui Road, Lanzhou, Gansu 730000, People’s Republic of ChinaEmail [email protected] ZhengNational Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 1 Yanchang Road, Lanzhou, Gansu 730000, People’s Republic of ChinaEmail [email protected]: The function of curcumin on the gastric cancer cell line, SGC-7901 is unknown. The present study aimed to observe the effects of curcumin on gastric cancer cells through the Shh and Wnt signaling pathways.Methods: SGC-7901 cells were transfected with si-Gli1 and si-β-catenin siRNA, then cells were stimulated with curcumin and its effects on cell migration, invasion, cytoskeleton remodeling, EMT, apoptosis and cell cycle were investigated by transwell assays, immunofluorescence and flow cytometry assays. The interaction between Gli1 and β-catenin was observed by co-immunoprecipitation.Results: We show that curcumin suppressed the expression of Shh, Gli1 and Foxm1 in the Shh signaling pathway, and the expression of β-catenin in the Wnt signaling pathway in SGC-7901 cells, both in mRNA and protein. As a result, cellular migration, invasion and cytoskeletal remodeling ability decreased. Our results revealed that when stimulated with curcumin, cells showed decreased cellular migration and invasion, while enhanced apoptosis. In addition, curcumin induced cytoskeletal remodeling and S phase cell cycle arrest. The inhibition of Shh and Wnt signaling pathway and the addition of curcumin also inhibited the epithelial–mesenchymal transition process. Furthermore, a physical interaction was observed between Gli1 of the Shh signaling and β-catenin of the Wnt signaling in these cells, but curcumin inhibited the interaction of these two proteins.Conclusion: The present study indicated that curcumin plays an anti-tumor role through Gli1-β-catenin pathway in gastric cancer SGC-7901 cells.Keywords: curcumin, Gli1, β-catenin, migration, invasion, cytoskeleton
