Cancer Management and Research (Jan 2020)
Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition
Abstract
Chien-Shan Cheng, 1, 2,* Jing-Xian Chen, 3, 4,* Jian Tang, 1, 2 Ya-Wen Geng, 1, 2 Lan Zheng, 3, 4 Ling-Ling Lv, 3 Lian-Yu Chen, 1, 2 Zhen Chen 1, 2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Traditional Chinese Medicine, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of China; 4Workstation of Xia Xiang, National Master of Traditional Chinese Medicine, Department of Traditional Chinese Medicine, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen Chen; Lian-Yu ChenDepartment of Integrated Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of ChinaTel +86-21-6417-5590 ext. 83628Email [email protected]; [email protected]: Paeonol, a natural product derived from the root of Cynanchum paniculatum (Bunge) K. Schum and the root of Paeonia suffruticosa Andr. (Ranunculaceae) has attracted extensive attention for its anti-cancer proliferation effect in recent years. The present study examined the role of paeonol in suppressing migration and invasion in pancreatic cancer cells by inhibiting TGF-β 1/Smad signaling.Methods: Cell viability was evaluated by MTT and colonial formation assay. Migration and invasion capabilities were examined by cell scratch-wound healing assay and the Boyden chamber invasion assay. Western Blot and qRT-PCR were used to measure the protein and RNA levels of vimentin, E-cadherin, N-cadherin, and TGF-β 1/Smad signaling.Results: At non-cytotoxic dose, 100 μ&Mgr; and 150 μ&Mgr; of paeonol showed significant anti-migration and anti-invasion effects on Panc-1 and Capan-1 cells (p< 0.01). Paeonol inhibited epithelial-mesenchymal-transition by upregulating E-cadherin, and down regulating N-cadherin and vimentin expressions. Paeonol inhibited TGF-β 1/Smad signaling pathway by downregulating TGF-β 1, p-Smad2/Smad2 and p-Smad3/Smad3 expressions. Further, TGF-β 1 attenuated the anti-migration and anti-invasion capacities of paeonol in Panc-1 and Capan-1 cells.Conclusion: These findings revealed that paeonol could suppress proliferation and inhibit migration and invasion in Panc-1 and Capan-1 cells by inhibiting the TGF-β 1/Smad pathway and might be a promising novel anti-pancreatic cancer drug.Keywords: paeonol, pancreatic adenocarcinoma, TGF-β 1/Smad signaling, epithelial-mesenchymal-transition, Cynanchum paniculatum
