CtBP2 promotes proliferation and reduces drug sensitivity in non-small cell lung cancer via the Wnt/ß-catenin pathway.

The C-terminal binding protein 2 (CtBP2) is crucial for the activation of the Wnt/ß-catenin pathway and regulates significant cellular processes in multiple cancer cells. However, the role of CtBP2 in non-small cell lung cancer (NSCLC) remains uncertain. Our western blotting and immunohistochemistry assays revealed that CtBP2 expression was obviously increased in NSCLC tissues and cells. In addition, the chi-square test and Kaplan-Meier analysis showed that over-expression of CtBP2 correlates with more invasive tumor phenotype and poor prognosis. In vitro studies with serum starvation-refeeding and CtBP2-shRNA transfection assay demonstrated that CtBP2 expression facilitates NSCLC cell proliferation and reduces sensitivity to cis-diamminedichloroplatinum (CDDP). The possible signaling transduction pathways were investigated, and the immunoprecipitation assay revealed that CtBP2 interacts directly with DvL1. Depletion of CtBP2 resulted in inhibited DvL1 expression and decreased expression of downstream genes. Moreover, our study showed that CtBP2 knockdown enhanced NSCLC cell sensitivity to CDDP through inhibition of the Wnt/ß-catenin pathway. These results suggest that CtBP2 plays a crucial role in NSCLC progression and CDDP sensitivity, and that CtBP2 depletion can provide a new target for NSCLC treatment.

[Expression and significance of FoxM1 in esophageal squamous cell carcinoma cells in vitro and in vivo].

OBJECTIVE: To investigate the expression and significance of FoxM1 in esophageal squamous cell carcinoma (ESCC) cell lines and tissues. METHODS: Western blot assay was used to detect the expression of FoxM1 in human esophageal epithelial cells and esophageal squamous cell cancer cell lines TE1, TE10, TE11 and Eca109 cells. To determine whether down-regulation of FoxM1 expression could inhibit the aggressive phenotype of ESCC cells, we knocked down the expression of FoxM1 by using FoxM1-shRNA in TE1 cells. Then we detected the cell proliferation, migration and invasion of TE1 cells by MTT assay, scratch assay and transwell assay. Furthermore, the effect of FoxM1 knockdown on tumorigenicity in nude mice was evaluated. Finally, immunohistochemical staining was used to detect the expression of FoxM1 in 99 cases of ESCC tissues and adjacent normal esophageal tissues. χ(2) test was used to analyze the correlations between the expression of FoxM1 and clinicopathologic characteristics and prognosis of ESCC patients. RESULTS: Western blot data showed that FoxM1 expression was lower in normal esophageal epithelial cells and highly expressed in four esophageal cancer cell lines, especially in TE1 cells. Knockdown of FoxM1 inhibited the growth, invasion and migration of TE1 cells and reduced their tumorigenicity in nude mice.The positive expression rate of FoxM1 in ESCC was 61.6% (61/99), significantly higher than that in the paired adjacent normal tissues (24.2%, 24/99) (P<0.05). The positive expression rate of FoxM1 in ESCC tissues was 61.6% (61/99), significantly higher than that in the paired adjacent normal tissues (24.2%, 24/99) (P<0.05). FoxM1 expression was significantly and positively correlated with lymph node metastasis, clinical stage and invasive depth (P<0.05). The median survival time was 42.3 months in 38 cases of patients with negative FoxM1 expression, and 33.0 months in 61 cases of positive FoxM1 expression, and the difference was statistically significant (P=0.036). CONCLUSIONS: FoxM1 is highly expressed in ESCC, and significantly correlated with the initiation, development and prognosis of esophageal cancer. FOXM1 might be an indicator to predict the prognosis and serve as a potential target for therapy in esophageal cancer.

Salidroside protects against premature senescence induced by ultraviolet B irradiation in human dermal fibroblasts.

OBJECTIVES: Salidroside, the predominant component of a Chinese herbal medicine, Rhodiola rosea L., becomes an attractive bio-agent due to its multifunction. Although it is well proposed that this herbal medicine may have photoprotective effect according to the folk hearsay, the direct supportive experimental evidences linking the drug with skin ageing have rarely been reported so far. The study was conducted to investigate the photoprotective role of salidrosdie and its related mechanisms in vitro. METHODS: First, a premature senescence model induced by UVB irradiation (250 mJ cm(-2)) in human dermal fibroblasts (HDFs) was established, and senescent phenotypes were evaluated by cell morphology, cell proliferation, senescence-associated beta-galactosidase (SA-ß-gal) activity and cell cycle distribution. Then the photoprotective effect of salidroside was investigated. Cells were pre-treated with various doses of salidroside (1, 5 and 10 µM) followed by the sublethal dosage of UVB exposure and then were harvested for various detections, including senescence-associated phenotypes and molecules, alteration of oxidative stress, matrix metalloproteinase-1 (MMP-1) secretion and inflammatory response. RESULTS: Pre-treatment of salidroside dose dependently reversed the senescent state of HDFs induced by UVB as evidenced by elevated cell viability, decreased SA-ß-gal activity and relieving of G1/G0 cell cycle arrest. UVB-induced increased protein expression of cyclin-dependent kinase (CDK) inhibitors p21(WAF) (1) and p16(INK) (4) was also repressed by salidrosdie treatment in a dose-dependent manner. Meanwhile, the increment of malondialdehyde (MDA) level in UVB-irradiated HDFs was inhibited upon salidroside treatment. Additionally, salidroside significantly attenuated UVB-induced synthesis of MMP-1 as well as the production of IL-6 and TNF-α in HDFs. CONCLUSION: Our data provided the evidences for the protective role of salidroside against UVB-induced premature senescence in HDFs probably via its anti-oxidative property and inhibition on production of MMP-1 and pro-inflammatory cytokines, which indicated its potential utilization as an active ingredient in the preparation of photoprotective formulation.

Association between variants of IL-8 and IL-10 genes, and efficacy of transcatheter arterial chemoembolization and subsequent prognosis in patients with liver cancer.

OBJECTIVE: Our objective was to examine the association between single nucleotide polymorphisms of interleukin (IL)-8 (rs4073 and rs2227306) and IL-10 (rs1800871 and rs1800872) genes, and clinical effects of transcatheter arterial chemoembolization (TACE) and subsequent prognosis in patients with liver cancer. PATIENTS AND METHODS: 115 patients with liver cancer underwent TACE. Venous blood specimens were collected for genomic DNA extraction. The restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) analysis was used to detect the above variants of IL-8 and IL-10 genes. In addition, blood levels of alpha fetal protein (AFP) were quantified by radioimmunoassay. Patients were followed up to uncover the association of the above genotypes with treatment efficacy and survival. RESULTS: Patients with the homozygous genotype AA or homozygous genotype TT (respectively, -251 and +781 sites) of IL-8 gene, and wild-type genotype TT or homozygous genotype AA (respectively, -819 and -592 sites) of IL-10 gene showed the best effectiveness of TACE. Furthermore, these patients also exhibited the lowest AFP levels and the longest survival after the treatment. CONCLUSIONS: Clinical efficacy of TACE and patient survival in liver cancer are associated with specific variants of IL-8 and IL-10 genes.