title: Galectin-3 induces ovarian cancer cell survival and chemoresistance via TLR4 signaling activation.
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.
authors.affiliation: 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.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Biliang
authors.initials: B
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: 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. weizoufumm@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D037502:Galectin 3 / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051242:Caveolin 1; D037502:Galectin 3; D015850:Interleukin-6; D016209:Interleukin-8; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A; D017239:Paclitaxel
keywords: Caveolin-1; Galectin-3; Ovarian cancer; Paclitaxel resistance; Toll-like receptor 4