Pseudolaric Acid B Inhibits Proliferation, Invasion and Epithelial-to-Mesenchymal Transition in Human Pancreatic Cancer Cell
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (19)
- Siegel RL, "Cancer statistics, 2015", CA Cancer J Clin, 65, pp.5~29 (2015)[DOI]
- Chen W, "Cancer statistics in China, 2015", CA Cancer J Clin, 66, pp.115~132 (2016)[DOI]
- Long J, "Cancer statistics: current diagnosis and treatment of pancreatic cancer in Shanghai, China", Cancer Lett, 346, pp.273~277 (2014)[DOI]
- Yang YM, "Epithelial-to-mesenchymal transition in the development of endometriosis", Oncotarget, 8, pp.41679~41689 (2017)
- Gu W, "Emergence of heterogeneous nuclear ribonucleoprotein A2", B1 vs loss of E-cadherin: their reciprocal immunoexpression profiles in human pancreatic cancer, 2013, pp.17, 14~17
- Yao GD, "Activation of p53 contributes to pseudolaric acid B-induced senescence in human lung cancer cells in vitro", Acta Pharmacol Sin, 37, pp.919~929 (2016)[DOI]
- Yu J, "Pseudolaric acid B activates autophagy in MCF-7 human breast cancer cells to prevent cell death", Oncol Lett, 11, pp.1731~1737 (2016)[DOI]
- Yu J, "Pseudolaric acid B inhibits proliferation in SW579 human thyroid squamous cell carcinoma", Mol Med Rep, 12, pp.7195~7202 (2015)[DOI]
- Sun Q, "The inhibitory effect of pseudolaric acid B on gastric cancer and multidrug resistance via Cox-2", PKC-<TEX>${\alpha}$<, P-gp pathway, pp.PLoS One, 2014[DOI]
- Zheng X, "Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer", Nature, 527, pp.525~530 (2015)[DOI]
- Rhim AD, "EMT and dissemination precede pancreatic tumor formation", Cell, 148, pp.349~361 (2012)[DOI]
- von Burstin J, "E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL", HDAC1, Gastroenterology, pp.2009, 137[DOI]
- Scheel C, "Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links", Semin Cancer Biol, 22, pp.396~403 (2012)[DOI]
- Wu K, "Slug contributes to cadherin switch and malignant progression in muscle-invasive bladder cancer development", Urol Oncol, 31, pp.1751~1760 (2013)[DOI]
- Vesuna F, "Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer", Biochem Biophys Res Commun, 367, pp.235~241 (2008)[DOI]
- Lamar JM, "The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain", Proc Natl Acad Sci U S A, 109, pp.E2441~E2450 (2012)[DOI]
- Yang N, "TAZ induces growth factor-independent proliferation through activation of EGFR ligand amphiregulin", Cell Cycle, 11, pp.2922~2930 (2012)[DOI]
- Shao DD, "KRAS and YAP1 converge to regulate EMT and tumor survival", Cell, 158, pp.171~184 (2014)[DOI]
- Karamitopoulou E, "Role of epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma: is tumor budding the missing link?", Front Oncol, 3, pp.221~ (2013)