Bufalin inhibits TGF-β-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-β receptors

Zhao,Lei; Liu,Shizhou; Che,Xiaofang; Hou,Kezuo; Ma,Yanju; Li,Ce; Wen,Ti; Fan,Yibo; Hu,Xuejun; Liu,Yunpeng; Qu,Xiujuan

doi:10.3892/ijmm.2015.2268

Bufalin inhibits TGF-β-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-β receptors

Authors:
- Lei Zhao
- Shizhou Liu
- Xiaofang Che
- Kezuo Hou
- Yanju Ma
- Ce Li
- Ti Wen
- Yibo Fan
- Xuejun Hu
- Yunpeng Liu
- Xiujuan Qu
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Affiliations: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: June 30, 2015 https://doi.org/10.3892/ijmm.2015.2268
Pages: 645-652
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The epithelial-to-mesenchymal transition (EMT) is a well-known prerequisite for cancer cells to acquire the migratory and invasive capacity, and to subsequently metastasize. Bufalin is one of the major active components of the traditional Chinese medicine Chan Su, and accumulating evidence has shown its anticancer effect in multipe types of cancer. However, the role of bufalin in transforming growth factor‑β (TGF‑β)‑induced EMT and migration remains unclear. In the present study, the effect of bufalin on TGF‑β‑induced EMT and migration was investigated in human lung cancer A549 cells. TGF‑β induced EMT in A549 cells and increased their migratory ability, which were markedly suppressed by bufalin. Additionally, TGF‑β‑induced upregulation of Twist2 and zinc finger E‑box binding homeobox 2 (ZEB2), as well as the phosphorylation of Smad2 and Smad3 were also inhibited by bufalin. However, the Smad‑independent signaling pathways were not affected. Further analysis showed that the TGF‑β receptor I (TβRI) and TGF‑β receptor II (TβRII) were downregulated in the presence of bufalin. Pretreatment with SB431542, a potent inhibitor of the phosphorylation of TβRI, significantly attenuated TGF‑β‑induced EMT, mimicking the effect of bufalin on A549 cells. Taken together, these results suggest that bufalin suppresses TGF-β-induced EMT and migration by downregulating TβRI and TβRII in A549 cells.

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