Open Access

Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail

  • Authors:
    • Shuo Fang
    • Ling Yu
    • Hongjun Mei
    • Jian Yang
    • Tian Gao
    • Anyuan Cheng
    • Weichun Guo
    • Kezhou Xia
    • Gaiwei Liu
  • View Affiliations

  • Published online on: November 2, 2016     https://doi.org/10.3892/ol.2016.5342
  • Pages: 5007-5014
  • Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

More than 30% of patients with osteosarcoma succumb to pulmonary metastases. Epithelial-mesenchymal transition (EMT) is a biological process by which tumor cells gain an increased capacity for invasiveness and metastasis. A previous study confirmed the phenomenon of EMT in osteosarcoma, a mesenchymal‑derived tumor. However, whether chemotherapy affects EMT remains to be elucidated. In the present study, the osteosarcoma cells were exposed to a sublethal dose of cisplatin, and any surviving cells were assumed to be more resistant to cisplatin. In addition, these cells exhibited a more mesenchymal phenotype. Immunofluorescence analysis revealed that the cisplatin treated cells had an increased long/short axis ratio and increased expression of N‑cadherin compared with control cells. A panel of EMT-associated genes was subsequently assessed by quantitative PCR and western blot analysis, and they were observed to be significantly upregulated in the cisplatin treated cells. The in vitro wound healing and Transwell assay indicated that the cisplatin treated cells were more prone to migrate and invade. An in vivo assay showed that the cisplatin‑treated xenograft had increased expression of EMT‑associated genes, and exhibited increased pulmonary lesions compared with the control, which indicated an elevated capacity to metastasize. The expression of Snail was knocked down by specific small interfering RNA, and it was observed that Snail inhibition promoted cisplatin sensitivity, and cisplatin‑induced EMT was significantly blocked. Taken together, the results of the present study supported that idea that Snail participates in cisplatin‑induced EMT in osteosarcoma cells, and targeting EMT-transcription factors may offer promise for the therapeutics of osteosarcoma.
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December-2016
Volume 12 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Fang S, Yu L, Mei H, Yang J, Gao T, Cheng A, Guo W, Xia K and Liu G: Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail. Oncol Lett 12: 5007-5014, 2016
APA
Fang, S., Yu, L., Mei, H., Yang, J., Gao, T., Cheng, A. ... Liu, G. (2016). Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail. Oncology Letters, 12, 5007-5014. https://doi.org/10.3892/ol.2016.5342
MLA
Fang, S., Yu, L., Mei, H., Yang, J., Gao, T., Cheng, A., Guo, W., Xia, K., Liu, G."Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail". Oncology Letters 12.6 (2016): 5007-5014.
Chicago
Fang, S., Yu, L., Mei, H., Yang, J., Gao, T., Cheng, A., Guo, W., Xia, K., Liu, G."Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail". Oncology Letters 12, no. 6 (2016): 5007-5014. https://doi.org/10.3892/ol.2016.5342