Abstract
Epithelial mesenchymal transition (EMT) is a critical process involved in the invasion and metastasis of cancer, including lung cancer (LC). Transforming growth factor (TGF)-β is one of factors capable of inducing EMT. Polyinosinic-polycytidylic acid (polyI:C), a synthetic agonist for toll-like receptor (TLR) 3, can enhance immune responses and has been used as an adjuvant for cancer vaccines; however, it remains unclear whether it influences other process, such as EMT. In the present study, we examined the effects of polyI:C on TGF-β-treated A549 human LC cells. By in vitro cell proliferation assay, polyI:C showed no effect on the growth of A549 cells treated with TGF-β1 at the concentration range up to 10μg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-β1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the 'cadherin switching'. The Akt inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C. PolyI:C has a novel function to suppress the motility of LC cells undergoing EMT by targeting the phosphatidylinositol 3-kinase/Akt pathway partly via PTEN and may prevent or reduce the metastasis of LC cells.
Highlights
By an in vitro cell proliferation assay, polycytidylic acid (polyI):C showed no effect on the growth of Transforming growth factor (TGF)-β1-treated A549 human lung cancer cells at the concentration range up to 10 mg/ml; it markedly suppressed the motility in a cell scratch and a cell invasion assay
The Ak strain transforming (Akt) inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the phosphatase and tensin homologue (PTEN)-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C
Our results indicate that polyI:C has the capacity to suppress the motility of TGF-β1-treated A549 cells by targeting the phosphatidylinositol 3-kinase /Akt pathway partly via PTEN and suggest that polyI:C may be used to prevent or reduce the metastasis of lung cancer cells
Summary
Methods and results: By an in vitro cell proliferation assay, polyI:C showed no effect on the growth of TGF-β1-treated A549 human lung cancer cells at the concentration range up to 10 mg/ml; it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-β1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the ‘cadherin switching’. The Akt inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C.
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