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Toll-like receptor 4 ligation confers chemoresistance to docetaxel on PC-3 human prostate cancer cells

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Abstract

Recent studies have indicated that Toll-like receptors (TLRs) are implicated in the development of chemoresistance in cancer cells. TLR4 has been shown to be highly expressed in prostate cancer cells and contributes to tumor cell survival and invasion. In this study, we aimed to investigate the role of TLR4 signaling in the chemoresistance of prostate cancer cells. We showed that ligation of TLR4 with lipopolysaccharide (LPS) abrogated docetaxel-induced growth suppression in PC-3 prostate cancer cells, with an increase in the half-maximal inhibitory concentration. Downregulation of TLR4 using small-interference RNA sensitized PC-3 cells to docetaxel-induced apoptosis as determined by annexin V staining and poly (ADP-ribose) polymerase cleavage, which was coupled with increased Bax expression and decreased Bcl-2. TLR4 ligation resulted in a marked increase in the phosphorylation of phosphatidylinositol 3-kinase (PI3-K) and Akt. The pretreatment with a PI3-K inhibitor LY294002 reduced LPS-mediated resistance to docetaxel, significantly decreasing the viability of PC-3 cells. Our data show that TLR4 ligation contributes to the chemosensitivity of prostate cancer cells, which at least partially involves the activation of the PI3-K/Akt pathway. Therefore, TLR4 signaling may represent a promising target for the improvement of chemotherapeutic efficacy in prostate cancer.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (30100185) and Natural Science Foundation of Shaan'xi Province of China (2009JQ4003).

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Authors and Affiliations

  1. Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

    Yuntao Zhang, Jianlin Yuan, Weijun Qin, Fei Liu, Fuli Wang, Geng Zhang & Xiaojian Yang

  2. Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, Shaanxi, China

    Yong Wang

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  1. Yuntao Zhang
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  2. Yong Wang
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Correspondence to Xiaojian Yang.

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Yuntao Zhang and Yong Wang contributed equally to this work.

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Zhang, Y., Wang, Y., Yuan, J. et al. Toll-like receptor 4 ligation confers chemoresistance to docetaxel on PC-3 human prostate cancer cells. Cell Biol Toxicol 28, 269–277 (2012). https://doi.org/10.1007/s10565-012-9221-2

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  • DOI: https://doi.org/10.1007/s10565-012-9221-2

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