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Oridonin inhibition and miR‑200b‑3p/ZEB1 axis in human pancreatic cancer.
- Source :
-
International journal of oncology [Int J Oncol] 2017 Jan; Vol. 50 (1), pp. 111-120. Date of Electronic Publication: 2016 Nov 18. - Publication Year :
- 2017
-
Abstract
- The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition (EMT) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array. The expression of miR‑200b-3p was verified by using real-time PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice and immunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer. We found that oridonin inhibited the proliferation of BxPC-3 and PANC-1 cells in a dose-dependent manner. miR-200b-3p was downregulated by oridonin in BxPC-3 and PANC-1 cells. ZEB1 was a target gene for miR-200b-3p. Oridonin or overexpression of miR‑200b-3p can inhibit the cell migration in BxPC-3 and PANC-1 cells. miR-200b-3p can inhibit the EMT and oridonin can inhibit the expression of ZEB1, N-cadherin and fibronectin but not increase the expression of E-cadherin, while the cell adhesion molecules ICAM-1 and VCAM-1 were decreased by oridonin in BxPC-3 and PANC-1 cells and the cytoskeleton was altered by oridonin in PANC-1 cells compared with the control. In summary, the results demonstrate that miR‑200b-3p was able to inhibit the EMT of human pancreatic cancer in vivo and in vitro by targeted ZEB1. In vitro, oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells, but not though type III EMT by miR-200-3p/ZEB1 axis, and may be related to type Ⅱ EMT, tumor microenvironment or altering the cytoskeleton. In vivo, oridonin inhibited the cancer migration in the nude mouse model though inhibiting EMT.
- Subjects :
- Animals
Cell Line, Tumor
Cell Movement drug effects
Cell Proliferation drug effects
Gene Expression Regulation, Neoplastic
Humans
Mice
MicroRNAs biosynthesis
Pancreatic Neoplasms genetics
Pancreatic Neoplasms pathology
Signal Transduction drug effects
Tumor Microenvironment
Zinc Finger E-box-Binding Homeobox 1 biosynthesis
Diterpenes, Kaurane administration & dosage
MicroRNAs genetics
Pancreatic Neoplasms drug therapy
Zinc Finger E-box-Binding Homeobox 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 50
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 27878247
- Full Text :
- https://doi.org/10.3892/ijo.2016.3772