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Targeting FoxM1 inhibits proliferation, invasion and migration of nasopharyngeal carcinoma through the epithelial‑to-mesenchymal transition pathway.
- Source :
-
Oncology reports [Oncol Rep] 2015 May; Vol. 33 (5), pp. 2402-10. Date of Electronic Publication: 2015 Mar 04. - Publication Year :
- 2015
-
Abstract
- High expression levels of the forkhead box M1 (FoxM1) transcription factor are associated with metastasis and poor prognosis of malignancies. However, little is known concerning its function in nasopharyngeal carcinoma (NPC). The present study aimed to investigate the impact of FoxM1 inhibition on the migration and invasion of NPC cells and the potential mechanisms. The effects of FoxM1 inhibitor treatment and FoxM1 silencing on the proliferation, migration and invasion of NPC CNE-1 and CNE-2 cells were examined by CCK-8, Transwell migration/invasion and colony formation assays. The effects of stable FoxM1 silencing on the growth and lung metastasis of implanted NPC were evaluated. The relative levels of FoxM1, zinc finger E-box binding homeobox 2 (ZEB2), Snail2 and E-cadherin in the different groups of NPC cells and tumors were determined by quantitative real-time PCR, western blotting and immunohistochemical assays. Treatment with thiostrepton, FoxM1 inhibitor, significantly reduced the survival of NPC cells. Treatment with thiostrepton and/or knockdown of FoxM1 inhibited the anchorage-independent proliferation, migration and invasion of NPC cells. Inhibition of FoxM1 also increased the relative levels of E-cadherin, but reduced ZEB2 and Snail2 expression in NPC cells. Stable FoxM1 silencing inhibited the growth and lung metastasis of implanted NPC in vivo, which was associated with increased levels of E-cadherin, but decreased ZEB2 and Snail2 expression in the NPC tumors. In conclusion, our data clearly indicate that knockdown of FoxM1 inhibited the growth and metastasis of human NPC by modulating epithelial-to-mesenchymal transition (EMT), and FoxM1 may be a potential target for the intervention of NPC.
- Subjects :
- Animals
Cadherins drug effects
Cadherins genetics
Cadherins metabolism
Carcinoma
Cell Line, Tumor
Cell Movement drug effects
Cell Movement genetics
Cell Proliferation drug effects
Cell Survival drug effects
Cell Survival genetics
Epithelial-Mesenchymal Transition drug effects
Forkhead Box Protein M1
Forkhead Transcription Factors antagonists & inhibitors
Gene Silencing
HEK293 Cells
Homeodomain Proteins drug effects
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Humans
Mice
Mice, Nude
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms pathology
Neoplasm Invasiveness
Neoplasm Transplantation
Repressor Proteins drug effects
Repressor Proteins genetics
Repressor Proteins metabolism
Reverse Transcriptase Polymerase Chain Reaction
Snail Family Transcription Factors
Thiostrepton pharmacology
Transcription Factors drug effects
Transcription Factors genetics
Transcription Factors metabolism
Zinc Finger E-box Binding Homeobox 2
Cell Proliferation genetics
Epithelial-Mesenchymal Transition genetics
Forkhead Transcription Factors genetics
Nasopharyngeal Neoplasms genetics
RNA, Messenger metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 33
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 25738652
- Full Text :
- https://doi.org/10.3892/or.2015.3834