Abstract
Abstract The mechanism of the negative regulation TGF-β mediated of epithelial-mesenchymal transition by sunitinib to inhibit ovarian cancer metastasis. We evaluated the inhibitory ability possessed by sunitinib against SKOV3 ovarian cancer cells motility by wound-healing and transwell assays. The results showed that sunitinib inhibited the migration of SKOV3 cells. The results obtained from wound-healing and transwell assays showed that sunitinib suppressed the motility of ovarian cancer SKOV3 cells in a concentration-dependent manner. In another,the effects of sunitinib on TGF-β-induced E-cadherin protein levels was assessed by western-blot, qRT-PCR and immunofluorescence assay. As a result, sunitinib attenuated the downregulation of E-cadherin protein level induced by TGF-β. Western-blot, qRT-PCR and immunofluorescence analyses displayed that the TGF-β stimulation reduced E-cadherin protein level, which could be attenuated by sunitinib. Our recent work reveals that the protein level of snail and the transcriptional activity of smad in sunitinib-treated cells were examined by western-blot and SBE-luciferase assay. Our results imply that sunitinib abolished TGF-β-induced upregulation of snail protein and decreased the transcriptional activity of smad complexes. The western-blot analyses revealed that sunitinib inhibited the upregulation of snail protein level caused by TGF-β treatment. The SBE reporter was constructed by linking the Smad-binding elements promoter upstream of luciferase reporter gene. A remarkable increment of transcriptional activity of Smads complexes was observed in SKOV3 cells exposed to TGF-β, which was significantly prohibited by sunitinib. The current study explores the prohibition of EMT, illustrates the anti-metastatic activities of sunitinib and the underlying mechanisms. [Keywords] Sunitinib; EMT; TGF-β; E-cadherin; Snail; Smad signal pathway Citation Format: Zibo Chen, Lin-lin Chang, Tian-yi Zhou, Dan-dan Wang, Ying Chen, Hong Zhu, Meidan Ying, Bo Yang, Qiao-jun He. Sunitinib suppresses ovarian cancer metastasis through the negative modulation of TGF-β-mediated epithelial-mesenchymal transition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5079.
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