Chimaphilin inhibits human osteosarcoma cell invasion and metastasis through suppressing the TGF-β1-induced epithelial-to-mesenchymal transition markers via PI-3K/Akt, ERK1/2, and Smad signaling pathways.
Epithelial-to-mesenchymal transition is a cellular process associated with cancer invasion and metastasis. However, the antimetastatic effects of chimaphilin remain elusive. In this study, we attempted to investigate the potential use of chimaphilin as an inhibitor of TGF-β1-induced epithelial-to-mesenchymal transition in U2OS cells. We found that TGF-β1 induced epithelial-to-mesenchymal transition to promote U2OS cell invasion and metastasis. Western blotting demonstrated that chimaphilin inhibited U2OS cell invasion and migration, increased the expression of the epithelial phenotype marker E-cadherin, repressed the expression of the mesenchymal phenotype marker vimentin, as well as decreased the level of epithelial-to-mesenchymal-inducing transcription factors Snail1 and Slug during the initiation of TGF-β1-induced epithelial-to-mesenchymal transition. In this study, we revealed that chimaphilin up-regulated the E-cadherin expression level and inhibited the production of vimentin, Snail1, and Slug in TGF-β1-induced U2OS cells by blocking PI-3K/Akt and ERK 1/2 signaling pathway. Additionally, the TGF-β1-mediated phosphorylated levels of Smad2/3 were inhibited by chimaphilin pretreatment. Above all, we conclude that chimaphilin represents an effective inhibitor of the metastatic potential of U2OS cells through suppression of TGF-β1-induced epithelial-to-mesenchymal transition.
a 3rd Department of Orthopedics, the First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin 150001, China.
Feng
F
Dong
b Pediatric Intensive Care Unit, the First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin 150001, China.
Tingting
T
Liu
a 3rd Department of Orthopedics, the First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin 150001, China.
Hao
H
Jin
a 3rd Department of Orthopedics, the First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin 150001, China.
Wenbo
W
Wang
D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014746:Vimentin / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D009285:Naphthoquinones; D051785:Smad Proteins; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C057774:chimaphilin
cellule d’ostéosarcome humaine; chimaphilin; chimaphiline; epithelial–mesenchymal transition; facteur de croissance transformant bêta 1; human osteosarcoma cell; metastasis; métastase; passage de l’état épithélial à l’état mésenchymateux; transforming growth factor beta1