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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.

No abstract

The aim of this study was to investigate c-Myc and β-catenin-mediated drug resistance in A549/DDP lung adenocarcinoma cells. Cisplatin sensitivity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) toxicity assay. β-Catenin and c-Myc protein expression following cisplatin treatment were determined using western blotting and immunofluorescence. Flow cytometry was performed to detect cell cycle and apoptosis in A549, A549/DDP, and c-Myc small interfering RNA (siRNA)-transfected A549/DDP cells before and after treatment with different doses of cisplatin. The median inhibitory concentration (IC50 ) in cisplatin-treated A549 and A549/DDP cells was 5.769 ± 0.24 μmol/L and 28.373 ± 0.96 μmol/L, respectively; the cisplatin resistance of A549 cells was about five times that of A549/DDP cells. Endogenous β-catenin and c-Myc expression in A549/DDP cells were higher than that in A549 cells, and were upregulated in A549/DDP cells (p < 0.05) and downregulated in A549 cells after 48 h cisplatin treatment (p < 0.05). β-catenin localization transferred from membrane/cytoplasmic/nuclear to cytoplasmic/nuclear, and c-Myc localization transferred from cytoplasmic/nuclear to nuclear in both cell lines following cisplatin treatment. The rate of apoptosis increased in a dose-dependent manner with cisplatin. After 48-h transfection with c-myc siRNA, A549/DDP cells were blocked in the S phase, and G0/G1-phase cells increased. Simultaneously, the apoptotic rate was increased (p < 0.05) and the IC50 decreased significantly (p < 0.05). C-myc, the downstream target gene of β-catenin, plays an important role in regulating cisplatin resistance in A549/DDP cells. C-Myc siRNA improved the sensitivity of A549/DDP cells to cisplatin.

No abstract

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its clinical significance in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed the expression pattern of Rsf-1 in human HCC tissues and found that Rsf-1 was overexpressed in 41.1 % of HCC specimens. There was a significant association between Rsf-1 overexpression and tumor stage (p = 0.0322), AFP (p = 0.0184), and tumor relapse (p = 0.0112). Furthermore, Rsf-1 overexpression correlated with poor overall survival in HCC patients (p < 0.001). Rsf-1 overexpression could serve as an independent predictor for poor recurrence-free survival (p = 0.0079). Small interfering RNA (siRNA) knockdown in SK-Hep-1 cells with high endogenous Rsf-1 expression inhibited cell proliferation and colony formation, with downregulation of cyclin E protein. In conclusion, Rsf-1 is overexpressed in HCCs and serves as a novel tumor marker. Rsf-1 contributes to hepatocellular carcinoma cell growth through regulation of cell cycle proteins.