The online version of this article (doi:10.1186/1476-4598-11-33) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
CFX designed the study and interpreted the data and amended the manuscript; CWT provided all the cell lines and gave instructions; SZJ performed the experiments and drafted the manuscript; LQQ participated in immunohistochemistry and flow cytometry analysis; and YDX helped to do the immunofluorescence microscope analysis. All of the authors read and approved the final version of this manuscript.
Toll-like receptor 4 (TLR4) is expressed on immune cells as a sensor that recognizes lipopolysaccharide (LPS), a microbial conserved component. It has recently been determined that the expression of TLR4 is also found in various types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral squamous cell carcinoma (OSCC) treatment. However, the mechanisms responsible for cisplatin resistance are not well understood.
The present study was designed to elucidate the role of TLR4 expression in human OSCC regarding immune escape and apoptotic resistance to cisplatin. TLR4 and the myeloid differentiation primary response gene 88 (MyD88) were highly expressed in OSCC cell lines. Upon LPS stimulation both NF-κB and p38 MAPK pathways were activated in OSCC cell lines, followed by the production of large quantities of IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells (HIOECs). OSCC cell lines were found to be resistant to cisplatin-mediated apoptosis after pretreatment with LPS.
Our results suggested that TLR4 was functionally expressed in human OSCC cells and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might thus elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC.
Additional file 1: Figure S1. HB and WSU-HN6 cells (5×105 ml-1) were stimulated with LPS (1 μg/ml) for 24 h, and then cytokine and chemokine in the supernatants were assayed using ELISA. Figure S2. LPS-induced secretion of cytokines was blocked by the specific p38 MAPK inhibitor PD169316. (XLS 32 KB)12943_2011_1035_MOESM1_ESM.xls
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- Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis
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