Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro

AIM: To investigate the effect and mechanism of blockade of the CXC chemokine receptor-4 (CXCR4) signaling pathway by AMD3100, a small non-peptide CXCR4 inhibitor, on invasion and metastasis of colorectal cancer cells in vitro. METHODS: Human colorectal cancer cell line SW480 was treated with AMD3100 at different final concentrations. 3-(4,5-dimethylthiazole-2-yl)-2.5-dipheny-ltetrazolium bromide (MTT) assay was used to detect the effect of AMD3100 on cell proliferation. The invasion ability of SW480 cells was determined by cell invasion assay kit. In the presence of AMD3100, the CXCL12-mediated migratory response of SW480 cells was tested by classical chemotaxis assays. RT-PCR analysis and Western blotting were used to detect the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in SW480 cells. RESULTS: Cell viability was significantly suppressed by AMD3100 in a dose-dependent manner. AMD3100 (100 and 1000 ng/mL) significantly inhibited the invasion ability of SW480 cells. Treatment with AMD3100 markedly reduced the expression of VEGF and MMP-9 but not MMP-2 in SW480 cells. CONCLUSION: The CXCL12/CXCR4 system is an important mediator of proliferation and invasion of CXCR4-expressing colorectal cancer cells. AMD3100 inhibited invasion and metastasis activity of the colorectalcancer cell line SW480 through down-regulation of VEGF and MMP-9 expression.

Peritoneal lavage cytology and carcinoembryonic antigen determination in predicting peritoneal metastasis and prognosis of gastric cancer

AIM: To evaluate the role of peritoneal lavage cytology (PLC) and carcinoembryonic antigen (CEA) determination of peritoneal washes (pCEA) in predicting the peritoneal metastasis and prognosis after curative resection of gastric cancer.METHODS: PLC and radioimmunoassay of CEA were performed in peritoneal washes from 64 patients with gastric cancer and 8 patients with benign diseases.RESULTS: The positive rate of pCEA (40.6%) was significantly higher than that of PLC (23.4%) (P<0.05).The positive rates of PLC and pCEA correlated with the depth of tumor invasion and lymph node metastasis (P<0.05). pCEA was found to have a higher sensitivity and a lower false-positive rate in predicting peritoneal metastasis after curative resection of gastric cancer as compared to PLC. The 1-, 3-, and 5-year survival rates of patients with positive cytologic findings or positive pCEA results were significantly lower than those of patients with negative cytologic findings or negative pCEA results (P<0.05). Multivariate analysis indicated that pCEA was an independent prognostic factor for the survival of patients with gastric cancer.CONCLUSION: Intraoperative pCEA is a more sensitive and reliable predictor of peritoneal metastasis as well as prognosis in patients with gastric cancer as compared to PLC method.

15-PGDH is reduced and induces apoptosis and cell cycle arrest in gastric carcinoma

AIM: To investigate the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in human gastric cancer and it's mechanism in apoptosis and cell cycle arrest. METHODS: Expression of 15-PGDH mRNA and protein was examined by immunohistochemistry, immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting in tissue from human gastric cancer, gastric precancerous state (gastric polyps and atrophic gastritis), normal stomach, and gastric cancer cell lines. The relationship between gastric cancer, gastric precancerous state and 15-PGDH expression was determined. The association between expression of 15-PGDH and various clinicopathological parameters in gastric cancer was evaluated. Human gastric cancer cell line SGC-7901 was transfected with 15-PGDH expression plasmids. The effect of 15-PGDH on the cell cycle was examined by flow cytometry. The effect of 15-PGDH on apoptosis was examined by transmission electron microscopy, flow cytometry and transferasemediated nick end labeling (TUNEL) assay. Expression of cell cycle (p21, p27, p16 and p53) and apoptosis (Survivin, BCL-2, BCL-XL, BAK and BAX) genes was analyzed by RT-PCR. RESULTS: Expression of 15-PGDH mRNA and protein in human gastric cancer tissues was significantly lower than in normal gastric tissues (P < 0.01). Expression in human gastric cancer cell lines MKN-28 and MKN-45 was reduced, and absent in SGC-7901 cells (P < 0.05). Reduction of 15-PGDH expression was also found in precancerous tissues, such as gastric polyps and atrophic gastritis (P < 0.01). There was a significant difference in expression of 15-PGDH among various gastric cancer pathological types (P < 0.05), with or without distant metastasis (P < 0.05) and different TNM stage (P < 0.01). Flow cytometry demonstrated a significant increase in apoptotic cells in SGC-7901 cells transfected with pcDNA3/15-PGDH plasmid for 24 and 48 h (P < 0.01), and an increased fraction of sub-G1 phase after transfection (P < 0.05). TUNEL assay showed an increased Apoptotic Index in cells overexpressing 15-PGDH (P < 0.01). After transfection, expression of proapoptotic genes, such as BAK (P < 0.05), BAX and p53 (P < 0.01), was increased. Expression of antiapoptotic genes was decreased, such as Survivin, BCL-2 and BCL-XL (P < 0.01). Expression of cyclin-dependent kinase inhibitors p21 and p16 (P < 0.01) was significantly upregulated in cells overexpressing 15-PGDH. CONCLUSION: Reduction of 15-PGDH is associated with carcinogenesis and development of gastric carcinoma. 15-PGDH induces apoptosis and cell cycle arrest in SGC-7901 cells.

Design and synthesis of hybrid solids based on the tetravanadate core toward improved catalytic properties

Five inorganic-organic hybrid vanadates based on tetravanadate cores, transition metals and N-donor ligands have been designed and synthesized under hydrothermal conditions, namely, [Zn（elM）312V4O12 （1）, [Zn（plM）3]2V4O12.H2O （2）, [Zn（iplM）3]2V4O12 （3）, [Co（eIM）3]2V4O12.H2o （4）, [Cu（eIM）2（H20）]2V4O12 （5） （eIM = 1-ethylimidazole, plM = 1-propylimidazole, ipIM = isopropylimidazole）. All compounds were fully characterized by single-crystal XRD, powder XRD, elemental analysis, TGA, and FT-IR spectroscopy. The hybrid zinc vanadates （1-3） and cobalt vanadate （4） exhibit interesting 2D folded structures and the hybrid copper vanadate （5） presents a 1D chain configuration. All compounds can catalyze olefin epoxidation reactions when using TBHP （TBHP = tert-butyl hydroperoxide） as an oxidant in acetonitrile. The introduction of transition metal ions into tetravanadate cores not only improved the catalytic activity but also fulfilled the heterogeneous catalytic behavior. 1-5 all exhibit extraordinary efficiency in converting olefins to the corresponding epoxides with high conversion and selectivity （particularly, cony. up to 97.1%, sele. up to 100% for 1 ）. Leaching test was also carried out to prove the heterogeneous behavior.