PDCD4 inhibits the malignant phenotype of ovarian cancer cells.

Programmed cell death 4 (PDCD4) is a newly identified tumor suppressor that can inhibit activator protein (AP)-1 activation and protein translation. Our previous studies indicate that lost or reduced PDCD4 expression is associated with the progression of ovarian carcinoma. However, direct evidence that PDCD4 inhibits malignant phenotype of human cancer cells is limited. In the present study, we found that PDCD4 expression in ovarian cancer cell lines (SKOV3, 3AO, and CAOV3) inhibited significantly their proliferation and cell cycle progression, and induced apoptosis. More importantly, up-regulation of PDCD4 expression decreased the colony-forming capacity of ovarian cancer cells in vitro and tumorigenic capacity in mice. These results demonstrate that PDCD4 can suppress the malignant phenotype of ovarian cancer cells, and may represent a novel therapeutic target for the treatment of ovarian cancer.

Detection of soluble TRAIL in HBV infected patients and its clinical implications.

AIM: To detect the expression of soluble TRAIL (TNF-related apoptosis inducing ligand, TRAIL) in the peripheral blood of HBV infected patients and try to elucidate whether the expression level of sTRAIL have any correlativity with the clinical staging, the expression level of HBV markers and the degree of liver damage. METHODS: 52 cases of HBV infected patients were investigated, including 8 HBV carriers, 30 chronic hepatitis B, 11 cirrhotics and 3 HBV infection related hepatocellular carcinoma. Expression of soluble TRAIL and markers of the hepatitis B were measured by enzyme-linked immunosorbent assay. RESULTS: The expression level of sTRAIL in the peripheral blood of the HBV infected patients was significantly higher than that of healthy controls (1378.35+/-540.23 pg/ml vs 613.75+/-175.80 pg/ml, P<0.001). In the group of chronic hepatitis, the expression level of sTRAIL was coincident with the status of the disease and was significantly correlated with the level of ALT. In the group of cirrhosis and liver cancer, its expression level was significantly higher than that of the healthy persons and HBV carriers, but lower than that of the hepatitis B patients; meanwhile, the expression of sTRAIL did not have any correlativity with the functional indexes of the liver. CONCLUSION: The soluble TRAIL in the HBV infected people may participate in the liver damage. Our results indicated that the expression level of soluble TRAIL may reflect the ravage of liver caused by host immune reaction to a certain degree.

[Correlation between sensitivity to TRAIL and expression level of DR5 on surface of tumor cells].

OBJECTIVE: To investigate the correlation between sensitivity to tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and expression level of death receptor 5 (DR5) on tumor cell surface. METHODS: Anti-DR5 mAb was used to detect expression level of DR5 on surface of tumor cells by flow cytometry. Sensitivity to apoptosis induced by TRAIL was determined by TRAIL apoptosis kit. The correlation between expression level of DR5 and sensitivity to TRAIL was analyzed. RESULTS: The expression of DR5 on surface of tumor cells was approximately 97.9% in U937 cells, 95.1% in Jurkat cells, 93.8% in SW480 cells, 86.2% in HCT116 cells, 64.2% in HL-60 cells, 46.6% in HeLa cells and 13.1% in K562 cells, respectively. The apoptosis rate induced by TRAIL was 72.6% in U937 cells, 85.2% in Jurkat cells, 78.6% in SW480 cells, 70.2% in HCT116 cells, 60.1% in HL-60 cells, 45.4% in HeLa cells and 12.3% in K562 cells, respectively. There was a significant positive correlation between the expression level of DR5 with TRAIL-inducing apoptosis (r = 0.997, P < 0.001). CONCLUSION: TRAIL-inducing apoptosis is related to the expression level of DR5 on surface of tumor cells. The results confirm the importance of DR5 expression for induction of apoptosis by TRAIL.