Yonsei Med J.  2018 Jan;59(1):20-27. 10.3349/ymj.2018.59.1.20.

Pseudolaric Acid B Inhibits Proliferation, Invasion and Epithelial-to-Mesenchymal Transition in Human Pancreatic Cancer Cell

Affiliations
  • 1Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. zhangcuiping753357@163.com
  • 2Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
  • 3Department of Hepatobiliary Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Abstract

PURPOSE
This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism.
MATERIALS AND METHODS
The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB.
RESULTS
PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups.
CONCLUSION
PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.

Keyword

PAB; PDAC; EMT; cell proliferation; Hippo-YAP pathway

MeSH Terms

Animals
Antineoplastic Agents/pharmacology/therapeutic use
Biomarkers, Tumor/metabolism
Cadherins
Cell Line, Tumor
Cell Movement
Cell Proliferation/drug effects
Cytokines
Deoxycytidine/analogs & derivatives/pharmacology/therapeutic use
Diterpenes/pharmacology/*therapeutic use
Epithelial-Mesenchymal Transition/*drug effects
Female
Humans
Mice, Nude
Neoplasm Invasiveness
Pancreatic Neoplasms/*diet therapy/*pathology
Real-Time Polymerase Chain Reaction
Signal Transduction/drug effects
Vimentin/metabolism
Antineoplastic Agents
Biomarkers, Tumor
Cadherins
Cytokines
Diterpenes
Vimentin
Deoxycytidine
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