No 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.

Abstract. LIM homeobox domain 6 (LHX6), a member of the LHX family of proteins, has been implicated in cancer development. However, the involvement of LHX6 in the development of breast cancer remains unclear. In the present study, the epigenetic regulation, biological function and associated molecular mechanisms of LHX6 in breast cancer were analyzed. The expression levels of LHX6 were demonstrated to be markedly decreased in breast cancer tissues and cell lines. In addition, it was found that increased LHX6 expression in breast cancer cell lines inhibited cell proliferation and invasion. Furthermore, increased LHX6 expression significantly decreased the expression of β-catenin in MDA-MB-231 breast cancer cells, and small interfering RNA-β-catenin enhanced LHX6-induced inhibition of cell proliferation and invasion in MDA-MB-231 breast cancer cells. These results indicate that LHX6 inhibits breast cancer cell growth and invasion through suppression of the Wnt/β-catenin signaling pathway. Thus, the present study provides a novel insight into the underlying mechanism of tumorigenesis in breast cancer, indicating the therapeutic potential of LHX6 in the treatment of breast cancer.

Rsf-1 (HBXAP) was recently reported to play roles in tumorigenesis and tumor progression. There have been many reports referred to Rsf-1 overexpression in various cancers and associated with the malignant behavior of cancer cells. However, the molecular mechanism of Rsf-1 in non-small cell lung cancer aggressiveness remains ambiguous. In the present study, we found that there was a significant association between Rsf-1 overexpression and poor overall survival (p = 0.028) in lung cancer. Furthermore, knockdown of Rsf-1 expression in H1299 and H460 cells with high endogenous Rsf-1 expression inhibited cell migration and invasion and downregulated MMP2 expression and nuclear levels of NF-κB. NF-κB inhibitor could also block the effect of Rsf-1 in regulation of MMP2 expression. Further experiments demonstrated that Rsf-1 depletion restrained NF-κB reporter luciferase activity and downregulated bcl-2 and p-IκB protein level. In conclusion, we demonstrated that Rsf-1 was overexpressed in lung cancer and associated with poor survival. Rsf-1 regulated cell invasion through MMP2 and NF-κB pathway.