Abstract
BackgroundOridonin (ORI) can inhibit proliferation and migration in various types of cancer cell lines. However, the exact mechanism remains unclear. We investigated the migration inhibitory effect of ORI on human pancreatic cancer SW1990 cells and dissected the possible molecular mechanism(s).MethodsCCK-8 assay was used to observe the cell viability. Wound healing assay, transwell assay and spontaneous metastasis model were used to observe the migration activities. Real-time PCR, immunofluorescence, western blot analysis and immunohistochemistry methods were used to observe the expression of genes or proteins.ResultsORI inhibited the migration of SW1990 cells. Real-time PCR and immuno-fluorescence analyses of epithelial-to-mesenchymal transition (EMT) markers were compared between control group and ORI group. The expression of mesenchymal molecular markers, such as vimentin, snail and slug decreased. The expression of epithelial-related marker E-cadherin increased. Wnt/β-catenin signalling was inhibited by ORI using luciferase reporter assay. ORI can decrease the β-catenin protein level not only in the nucleus, but also in the cytoplasm and the whole cell after the treatment with ORI and glycogen synthase kinase 3β (GSK3β) was increased in the ORI-treated group. CHIR could attenuate the effects of ORI in SW1990 cells. We established a mice model by injecting 1 × 106 SW1990 cells into nude mice intraperitoneally to test whether ORI affects tumour metastasis. Metastatic formation was inhibited by ORI (5 and 10 mg/kg) compared with the control group. Tumour sections stained with anti-E-cadherin, anti-vimentin and anti-β-catenin antibodies revealed that ORI inhibited EMT, as well as the Wnt/β-catenin pathway in vivo.ConclusionsORI can inhibit pancreatic cancer cell SW1990 migration and EMT by down-regulating Wnt/β-catenin signal transduction in vitro and in vivo. Therefore, it can be potentially and effectively used in the clinical management of pancreatic cancer.
Highlights
Oridonin (ORI) can inhibit proliferation and migration in various types of cancer cell lines
We decided to use this cell line, which was derived from a spleen metastasis of a grade II pancreatic adenocarcinoma [13], to evaluate the role of ORI in pancreatic cancer metastasis and epithelial-to-mesenchymal transition (EMT)
The results indicated that ORI can decrease the β-catenin protein level in the nucleus, Fig. 2 Impact of ORI on EMT of tumor cells. a Real-time PCR analysis of EMT markers were compared between control group and ORI group (15 μM)
Summary
Oridonin (ORI) can inhibit proliferation and migration in various types of cancer cell lines. We investigated the migration inhibitory effect of ORI on human pancreatic cancer SW1990 cells and dissected the possible molecular mechanism(s). EMT-induced adenocarcinoma cells can acquire malignant features, such as invasion, metastatic capabilities and chemo-resistance [3, 4]. In human pancreatic tumour samples, fibronectin and vimentin are increased in high-grade tumours, with a corresponding decrease in E-cadherin expression. These patients have worse prognoses than those who demonstrate less evidence of EMT. Numerous signalling pathways that are involved in the regulation of EMT, such as transforming growth factorbeta, notch and Wnt signalling pathways, are highly activated in metastatic pancreatic cancers and appear to be associated with prognosis [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
