Knockdown of S100A4 chemosensitizes human laryngeal carcinoma cells in vitro through inhibition of Slug

D.-P. Liang, T.-Q. Huang, S.-J. Li , Z.-J. Chen

Otolaryngology, the Affiliated Hospital of Qingdao University, Qingdao, China. chenzhijun2014715@126.com

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• Oncology

OBJECTIVE: S100A4 and Slug are known to be closely involved in resistance to chemotherapy. Furthermore, Slug signal was regulated by S100A4. Targeted therapy reducing S100A4 expression and Slug pathway activity may overcome the chemoresistance of human cancers. We hypothesized that over-expression of S100A4 and Slug was associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether S100A4 silencing inhibited Slug, resulting in sensitization of laryngeal carcinoma Hep-2 cells to cisplatin.

MATERIALS AND METHODS: We investigated the effects of S100A4 and Slug silencing by siRNA transfection on chemosensitivity to cisplatin (DDP) in Hep-2 cells in vitro. In order to confirm the correlation between S100A4 and Slug signals, siRNA transfected Hep-2 cells were over-expressed by pSlug transfection, then explored the effect of S100A4 silencing on chemosensitivity to cisplatin (DDP) in Hep-2 cells in vitro. Real-time RT-PCR and Western blotting confirmed the presence of S100A4 mRNA, Slug mRNA and proteins in Hep-2 cells.

RESULTS: We found that resistance or insensitivity of Hep-2 cells to cisplatin might be associated with S100A4 and Slug expression. Knockdown of S100A4 and Slug markedly enhanced the cisplatin-induced suppression of Hep-2 cell growth and increased apoptosis. Knockdown of S100A4 may significantly reduce the levels of S100A4 mRNA, Slug mRNA and proteins, in cisplatin-treated Hep-2 cells. Re-expression of Slug in S100A4 siRNA transfected Hep-2 cells restored the cisplatin resistance in the Hep-2 cells.

CONCLUSIONS: Overexpression of S100A4 may be associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. Knockdown of S100A4 enhances the sensitivity to cisplatin of laryngeal carcinoma cells via inhibition of Slug expression.

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