Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition

Purpose: 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-beta 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-beta 1/Smad signaling. Results: At non-cytotoxic dose, 100 mu M and 150 mu M of paeonol showed significant antimigration 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-beta 1/Smad signaling pathway by downregulating TGF-beta 1, p-Smad2/Smad2 and p-Smad3/Smad3 expressions. Further, TGF-beta 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-beta 1/Smad pathway and might be a promising novel anti-pancreatic cancer drug.