title: Galectin-3 regulates metastatic capabilities and chemotherapy sensitivity in epithelial ovarian carcinoma via NF-κB pathway.
abstract: Galectin-3 (Gal-3) has been found to be involved in the tumor progression and chemoresistance of epithelial ovarian cancer (EOC). Some studies have shown that Gal-3 may interact with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). However, it is unclear whether the effects of Gal-3 on the metastasis and chemosensitivity of EOC are related to NF-κB. In this study, we aimed to explore whether Gal-3 promoted progression and carboplatin resistance in EOC via NF-κB pathway. Plasmid transfection and RNA interference were used to upregulate or downregulate the expression of Gal-3 in ovarian cancer cell lines. Then, the expression of Gal-3 and the protein expressions of phosphorylation NF-κB pathway molecules were further detected by Western blot. Transwell migration assay was employed to detect the effects of Gal-3 on the migration and invasion of ovarian cancer cell lines. After treatment with carboplatin, flow cytometry (FCM) was employed to detect the effects of Gal-3 on carboplatin-induced apoptosis. Immunofluorescence technique was used to examine the translocation of phosphorylated P65 into the nucleus in ovarian cancer cells after the upregulation of Gal-3. After the knockdown of Gal-3 by small interfering RNA (siRNA), the migration and the invasion of cancer cells were significantly inhibited while the apoptosis and the sensitivities to carboplatin increased. Western blot showed reduction in the phosphorylation components of the NF-κB pathway: inhibitor of kappa B (IκB), IκB kinase (IKK), and P65. However, after the Gal-3 upregulation by plasmid transfection, the capabilities of migration and invasion of cancer cells were significantly promoted while the apoptosis and the sensitivities to carboplatin decreased. Immunofluorescence showed increased nuclear translocation of P65. Inhibitors of the NF-κB pathway did not affect the Gal-3 expression level in ovarian cancer cells. Gal-3 may affect the migratory and invasive capabilities of cancer cells as well as the chemosensitiviy to carboplatin in EOC by acting through the NF-κB pathway.
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China.
authors.forename: Huaiwu
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China.
authors.forename: Guocai
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China.
authors.forename: Miaofang
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, West Yan-jiang Road, 510120, Guangzhou, China. linzhongqiusysu@163.com.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Ameritech Biomedicines, Inc., Houston, TX, 77509, USA.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Inserm U1059, Saint-Etienne, 42023, France.|CHU Saint-Etienne, Plateau de Biologie, Saint-Etienne, 42055, France.
authors.forename: Guorong
authors.initials: G
authors.lastname: Li
mesh_terms: D017209:Apoptosis; D001798:Blood Proteins; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D037502:Galectin 3 / Q000378:metabolism*; D037161:Galectins; D006801:Humans; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
chemical_list: D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D016328:NF-kappa B
keywords: Carboplatin chemoresistance; Epithelial ovarian cancer; Galectin-3; NF-κB; Pathway