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.

Galectins-1, -3, and -7 Are Prognostic Markers for Survival of Ovarian Cancer Patients

“…In cholangiocarcinoma, Gal-3 expression was associated with a poorly-differentiated type, while in vitro experiments showed significantly increased cell migration and invasion after suppression of Gal-3 expression [32]. However, for ovarian cancer, in vitro experiments showed knockdown of Gal-3 inhibits migration and invasion of cancer cells, while apoptosis and sensitivity to carboplatin increases [33]. Moreover, paclitaxel and additional Gal-3 inhibitor treatment showed synergistic cytotoxic effects and increased apoptosis in an on ovarian cancer cell line [34].…”

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

“…Inhibition of galectin expression, using siRNA or antisense sequences, showed significant results in colon [233], ovarian [234], esophageal [235], hepatocarcinoma [236], glioma [237], glioblastoma [238], and melanoma [239] cell lines. Anti-galectin mAbs and Gal-3 recombinant were also effective in vitro studies with diverse cell lines [240-242].…”

Galectin-3 Induces a Pro-degradative/inflammatory Gene Signature in Human Chondrocytes, Teaming Up with Galectin-1 in Osteoarthritis Pathogenesis

“…However, exposure to sodium nitroprusside, which impairs NF-κB activation in human OA chondrocytes, led to a decrease in Gal-3, further exacerbated by three types of NF-κB-targeting inhibitors34. When looking at other cell types, Gal-3 is an upstream regulator of the NF-κB pathway in acute lymphoblastic leukemia42 and ovarian cancer cells43, also critically responsible for stimulation of IL-6 and CCL5 production/secretion from synovial fibroblasts of RA and – to a lesser extent – of OA patients44. Its truncated form appears to be able to reduce phosphorylation of p65/IκB in multiple myeloma and ovarian cancer cells43.…”

“…When looking at other cell types, Gal-3 is an upstream regulator of the NF-κB pathway in acute lymphoblastic leukemia42 and ovarian cancer cells43, also critically responsible for stimulation of IL-6 and CCL5 production/secretion from synovial fibroblasts of RA and – to a lesser extent – of OA patients44. Its truncated form appears to be able to reduce phosphorylation of p65/IκB in multiple myeloma and ovarian cancer cells43. In our assays, this natural variant was not active as elicitor and did not interfere with galectin activity (not shown).…”