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Kawasaki, Japan

Xiu Y.-L.,Shenyang University | Zhao Y.,Shenyang University | Gou W.-F.,Institute of Pathology and Pathophysiology | Chen S.,Shenyang University | And 2 more authors.
PLoS ONE | Year: 2014

Background: Anacardic acid (AA) is a mixture of 2-hydroxy-6-alkylbenzoic acid homologs. Certain antitumor activities of AA have been reported in a variety of cancers. However, the function of AA in ovarian cancer, to date, has remained unknown. Methods: Ovarian cancer cell lines were exposed to AA, after which cell proliferation, apoptosis, invasion and migration assays were performed. Phalloidin staining was used to observe lamellipodia formation. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were used to assess the mRNA and protein expression levels of Phosphatidylinositol 3-kinase (PI3K), vascular endothelial growth factor (VEGF) and caspase 3. Results: Our results showed that AA promotes ovarian cancer cell proliferation, inhibits late apoptosis, and induces cell migration and invasion, as well as lamellipodia formation. AA exposure significantly up-regulated PI3K and VEGF mRNA and protein expression, while, in contrast, it down-regulated caspase 3 mRNA and protein expression in comparison to untreated control cells. Conclusion: Taken together, our results demonstrate for the first time that AA may potentiate the proliferation, invasion, metastasis and lamellipodia formation in ovarian cancer cell lines via PI3K, VEGF and caspase 3 pathways. © 2014 Xiu et al.

Chen S.,Shenyang University | Zhao Y.,Shenyang University | Gou W.-F.,Shenyang Medical College | Zhao S.,Shenyang Medical College | And 2 more authors.
PLoS ONE | Year: 2013

Histone deacetylase inhibitors (HDACi), such as suberoylanilide hydroxamic acid (SAHA), have been shown to act selectively on gene expression, and are potent inducers of growth arrest, differentiation and apoptosis in various types of cancers in vitro and in vivo. This study aimed to elucidate the anti-tumor effects and molecular mechanisms of SAHA on the aggressive phenotypes of ovarian carcinoma. Two pairs of cell lines (SKOV3 and SKOV3/DDP; HO8910 and HO8910-PM) were exposed to SAHA treatment, and the effects on acetyl-Histone H3 and H4 expression levels were analyzed and compared against the aggressive behaviors of ovarian carcinoma. Our results showed that SAHA suppressed proliferation in both a concentration- and time-dependent manner in all four cell lines; induced S/G2 arrest in SKOV3 and SKOV3/DDP cells; and conversely, induced G1 arrest in HO8910 and HO8910-PM cells. SAHA treatment induced apoptosis and reduced migration, invasion and lamellipodia formation in the ovarian carcinoma cells; furthermore, SAHA decreased expression of Cyclin B1 and CDC2P34 mRNA, and downregulated CDC2P34, Erk1/2, CyclinB1 and MMP-9 proteins. In contrast, SAHA increased expression of Caspase-3, p21 and p53 mRNA, and upregulated acetyl-Histones H3 and H4, Caspase-8, and p53 proteins. Basal acetylation of histone H3 and H4 was higher in ovarian carcinoma compared to normal ovarian tissues and benign ovarian tumors, and in borderline tumor than in normal ovarian tissues, and was positively correlated with differentiation and expression of the proliferative marker, Ki-67 (P < 0.05). We suggest that SAHA may suppress growth, migration and invasion in ovarian carcinoma cells, including cisplatin-resistant or highly-invasive ovarian cells, by promoting histone acetylation and modulating their phenotype-related molecules. As such, aberrant acetylation of histone H3 and H4 may play an important role in the carcinogenesis and differentiation of ovarian carcinoma. © 2013 Chen et al.

Zhao Y.,Shenyang University | Chen S.,Shenyang University | Gou W.-F.,Shenyang University | Xiao L.-J.,Shenyang University | And 2 more authors.
Tumor Biology | Year: 2014

Beclin 1, an important autophagy-related protein in human cells, is involved in autophagy, differentiation, anti-apoptosis, and cancer suppression, which is increased during periods of cell stress and extinguished during cell cycle. Human ovarian tumors display allelic loss of Beclin 1 with high frequency. To clarify Beclin 1's role in ovarian carcinogenesis and subsequent progression, its expression was examined by immunostaining on tissue microarrays containing ovarian normal tissue, benign and borderline tumors, and carcinomas. Beclin 1 mRNA and protein expression was examined in ovarian normal tissue, benign and borderline tumors, carcinoma tissue, and cell lines by reverse transcription polymerase chain reaction or Western blot, respectively. The results demonstrated that the higher Beclin 1 mRNA was observed in ovarian benign tumor than normal ovary and ovarian carcinoma (P < 0.05) and negatively correlated with the differentiation of ovarian carcinoma (P < 0.05). Beclin 1 protein expression was stronger in ovarian carcinoma than that in normal ovary and inversely related to the differentiation of ovarian carcinoma (P < 0.05) by Western blot. Immunohistochemically, Beclin 1 expression was statistically higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumor (P < 0.05) and inversely linked to differentiation, lower ki-67 expression, and higher cumulative or relapse-free survival rate of ovarian carcinoma (P < 0.05). Cox proportional hazard model indicated that age and International Federation of Gynecology and Obstetrics staging (P < 0.05), but not pathological classification differentiation degree or Beclin 1 expression, were independent prognostic factors for overall and relapse-free ovarian carcinomas (P > 0.05). It was suggested that the aberrant Beclin 1 expression is closely linked to tumorigenesis and differentiation of ovarian carcinoma. Beclin 1 expression might be employed to indicate the worse prognosis of ovarian carcinomas, albeit not an independent factor. © 2013 International Society of Oncology and BioMarkers (ISOBM).

Xiao L.-J.,Chengde Medical University | Zhao E.-H.,Chengde Medical University | Zhao S.,Chengde Medical University | Zheng X.,Chengde Medical University | And 3 more authors.
Oncology Letters | Year: 2014

Paxillin encodes a focal adhesion-associated protein and is involved in the progression and aggressive phenotypes of malignancies through its interactions with the actin cytoskeleton and key signal transduction oncogenes. The present study aimed to investigate the clinicopathological and prognostic significance of paxillin in gastric cancer. The expression of paxillin was evaluated using tissue microarrays of gastric adjacent non-cancerous mucosa, adenoma and carcinoma specimens by immunohistochemistry. Paxillin expression was compared against clinicopathological parameters and the survival time of the patients. Paxillin was highly expressed in gastric adenoma compared with that in non-neoplastic mucosa and carcinoma (P<0.05). Paxillin expression was lower in the younger carcinoma patients compared with that in the elder carcinoma patients (P<0.05). Paxillin expression was negatively correlated with tumor size, depth of invasion and lymph node metastasis, but not with patient gender, lymphatic or venous invasion, or TNM staging (P>0.05). Higher paxillin expression was observed in intestinal-type compared with diffuse-type carcinoma (P<0.05). Kaplan-Meier analysis indicated a positive association between paxillin expression and cumulative survival rate in all, advanced and intestinal-type carcinoma patients (P<0.05). Multivariate analysis using the Cox proportional hazards model indicated that patient age, depth of invasion, lymphatic invasion, lymph node metastasis, TNM staging and Lauren classification were independent prognostic factors for all gastric carcinomas (P<0.05). Aberrant paxillin expression may be involved in the growth, invasion, metastasis and differentiation of gastric carcinoma. Altered paxillin expression may, therefore, be employed as an indicator of pathobiological behaviors and prognosis of gastric carcinomas.

Deng B.,Shenyang University | Zhao Y.,Shenyang University | Gou W.,Shenyang Medical College | Chen S.,Shenyang University | And 3 more authors.
Tumor Biology | Year: 2013

B-cell translocation gene 3 (BTG3) is a member of the BTG family which inhibits cell proliferation, metastasis, and angiogenesis, and also regulates cell-cycle progression and differentiation in a variety of cell types. However, there is no study to analyze BTG3 expression in epithelial ovarian carcinoma (EOC). Here, we investigated the expression of BTG3 in EOC carcinogenesis and subsequent progression. BTG3 mRNA expression was detected by real-time RT-PCR in ovarian benign and malignant tumors. The expression of BTG3 protein was examined by immunohistochemistry on tissue microarrays containing ovarian normal tissue, benign and borderline epithelial ovarian tumors, and EOCs. Relationships of BTG3 with both EOC clinicopathology and prognosis were analyzed statistically. The expression of BTG3 protein was also evaluated in ovarian normal tissue, benign tumors, and EOCs by western blot. The BTG3 mRNA expression level was higher in ovarian normal tissue and benign tumors than that in borderline, primary, and metastatic carcinoma (p < 0.05), and was negatively correlated with dedifferentiation and FIGO staging of EOC (p < 0.05). Using western blot, BTG3 protein was found lower in EOCs compared to the normal and benign tumors (p < 0.05), and poorly differentiated EOCs showed lower BTG3 expression than well-differentiated and moderately differentiated EOCs (p < 0.05). Immunohistochemically, BTG3 protein expression was statistically lower in EOCs than normal tissue and benign tumors (p < 0.05). EOC patients with low BTG3 protein expression showed a higher incidence of metastasis (p = 0.020), poor differentiation (p = 0.030), and shorter disease-free time and overall survival time (p < 0.05). By using Cox's proportional hazard model, BTG3 protein expression and FIGO staging were independent prognostic factors for both disease-free time and overall survival time of EOCs (p < 0.05). It was suggested that down-regulated BTG3 expression might play roles in the pathogenesis and aggressiveness of EOC. BTG3 protein expression may be considered as a good marker to indicate the favorable prognosis of EOCs. © 2013 The Author(s).

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