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Galectin-3 induces ovarian cancer cell survival and chemoresistance via TLR4 signaling activation

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Tumor Biology

Abstract

Paclitaxel resistance becomes common in patients with aggressive ovarian cancer and results in recurrence after conventional therapy. Galectin-3 is a multifunctional lectin associated with cell migration, cell proliferation, cell adhesion, and cell-cell interaction in tumor cells. Whether circulating galectin-3 is involved in paclitaxel resistance in ovarian cancer remains unknown. The current study investigated the effect of galectin-3 on toll-like receptor 4 (TLR4) signaling and thus paclitaxel resistance. With blood and cancer tissue samples obtained from 102 patients, we identified associations between serum galectin-3 level or TLR4 expression and paclitaxel resistance phenotype. In vitro, treatment with exogenous galectin-3 restored cell survival and migration of SKOV-3 and ES-2 cells was decreased by galectin-3 silencing and paclitaxel treatment. Furthermore, exogenous galectin-3 boosted expression of TLR4, MyD88, and p-p65, as well as interleukin (IL)-6, IL-8, and vascular endothelial growth factor (VEGF) release induced by paclitaxel. Moreover, galectin-3 inhibited the interaction between TLR4 and caveolin-1 (Cav-1) in SKOV-3 and ES-2 cells. In addition, overexpression of Cav-1 dampened the expression of MyD88 and p-p65 stimulated by galectin-3 and enhanced apoptosis in SKOV-3 cells under paclitaxel exposure. In summary, our study elucidated that exogenous galectin-3 might induce paclitaxel resistance through TLR4 signaling activation by inhibiting TLR4-Cav-1 interaction, revealing a novel insight into paclitaxel resistance induction.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81101959 and 81101958).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, No. 127 West Changle Road, Xincheng District, Xi’an, 710032, People’s Republic of China

    Guoqing Cai, Xiangdong Ma, Biliang Chen, Yanhong Huang, Shujuan Liu, Hong Yang & Wei Zou

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  1. Guoqing Cai
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  2. Xiangdong Ma
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  4. Yanhong Huang
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  6. Hong Yang
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  7. Wei Zou
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Corresponding author

Correspondence to Wei Zou.

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This study was reviewed by the Ethics Committee of Xijing Hospital, the Fourth Military Medical University, and was performed in accordance with the Helsinki Declaration. Written informed consent was obtained from the patients enrolled in our study.

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Cai, G., Ma, X., Chen, B. et al. Galectin-3 induces ovarian cancer cell survival and chemoresistance via TLR4 signaling activation. Tumor Biol. 37, 11883–11891 (2016). https://doi.org/10.1007/s13277-016-5038-6

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  • DOI: https://doi.org/10.1007/s13277-016-5038-6

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