Journal
CANCER MANAGEMENT AND RESEARCH
Volume 12, Issue -, Pages 641-651Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/CMAR.S224416
Keywords
paeonol; pancreatic adenocarcinoma; TGF-beta 1/Smad signaling; epithelial-mesenchymal-transition; Cynanchum paniculatum
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Funding
- National Natural Science Foundation of China [81573752, 81603444]
- Shanghai Science and Technology Committee Project [15401932500]
- Workstation of Xia Xiang, National Master of Traditional Chinese Medicine from the State Administration of Traditional Chinese Medicine of the People's Republic of China
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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.
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