COX-2 induced angiogenesis and peritoneal adhesion / 国际外科学杂志

Postoperative peritoneal adhesion represents a major complication of surgery. Recently, the angiogenesis which cyclooxygenase-2 enzyme induced was found to play an important role in the adhesion synthesis. This review summarized the relationship between COX-2 induced angiogenesis and peritoneal ad- hesion.

Effects of selective Cox-2 inhibitor in preventing postoperative recurrence of colorectal cancer / 上海第二医科大学学报

0.05),but the 3-year recurrent rates were significantly different(P

Inhibitory Effect on Angiogenesis of a Selective Cyclooxygenase-2 Inhibitor with using Mouse Mammary Tumor cells / 한국유방암학회지

PURPOSE: Angiogenesis plays a key role in the growth and metastasis of malignant tumor. Angiogenesis is reportedly enhanced by prostaglandins (PGs). Cyclooxygenase (COX)-2 is an inducible enzyme that catalyzes the formation of PGs from arachidonic acid. The COX enzyme system is composed of two isoenzymes, COX-1 and COX-2. Recent sources of experimental and epidemiological evidence suggest a significant role for the COX enzymes, particularly COX-2, in the pathogenesis of breast cancer. COX-2 overexpression in a murine mammary gland is sufficient to cause tumor formation. We performed our study to determine the effect of COX-2 inhibitor in a in vivo mouse mammary tumor (MMT) cell line. METHODS: In order to test our study, 24 C57BL/6 type mice (Jackson Laboratory, Bar Harbor, USA) were randomized to receive 35 days of either placebo supplemented diet (n=11) or a 1,500ppm celecoxib (CELEBREX, Pfizer Inc. St. Louis, USA) supplemented diet (n=13) beginning at day 0. At 14 days after the beginning day, 30 microliter of a 1% India ink solution that contained 500,000 of MMT cells or dye alone (control) was intradermally inoculated at each flank (day 14). The animals were sacrificed 21 days later (day 35) and skin specimens were harvested/processed for quantification of the microvessel density (MVD) that was associated with each inoculated site. The aortas that were isolated according to each treatment group at the time of animal sacrifice were used to create identical aortic ring angiogenesis assays (media 199 supplemented with 20% FBS). Explants were evaluated for 14 days in culture to determine both the rate of angiogenesis initiation (% of explants exhibiting the angiogenic phenotype) and the neovessel growth rate (using a subjective angiogenic index score for the wells exhibiting initiation). Analysis of variance (ANOVA) was used to evaluate the differences between groups for each assay. RESULTS: According to the immunohistochemical staining, celecoxib administration resulted in a parallel decrease in the MVD at both the control and MMT inoculated sites (22% and 21%, p = 0.025 and p = 0.010 respectively). On the aortic ring assay, the dietary treatment group was not significantly inhibited compared with the placebo group (75% and 63.3%, respectively, p = NS). However, dietary celecoxib administration significantly inhibited the angiogenic index of the neovessel growth rate (5.0 +/- 2.38 and 8.9 +/- 3.44, respectively, p < 0.001). CONCLUSION: These results suggest that a selective COX-2 inhibitor had an antiangiogenic effect on the in vivo tumor cells. We will perform more investigations of a selective COX-2 inhibitors, and these may will be crucial drugs to use as new chemotherapy agents for treating in cancer.

The Modulation of Radiosensitivity by Combined Treatment of Selective COX-2 Inhibitor, NS 398 and EGF Receptor Blocker AG 1478 in HeLa Cell Line / 대한방사선종양학회지

PURPOSE: Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. MATERIASL AND METHODS: Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy (SF2) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. RESULTS: A cooperative effect were observed on the apoptosis of the HeLa cell line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of 22.70% compare with combination of the one drug with radiation, apoptosis of 8.49 %. In cell cycle analysis, accumulation of cell on G0/G1 phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity in a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and SF2 of 0.12 but the combination of one drug with radiation was not enhanced radiosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. CONCLUSION: Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

The inhibitory effect of cyclooxygenase inhibitor on human breast cancer line MDA-MB-231 in vitro / 重庆医科大学学报

Objective:To investigate the inhibitory effect of cyclooxygenase inhibitor acetylsalicylic acid(ASA),and a selective COX-2 inhibitor(Nimesulide) on the growth of human breast cancer cell line MDA-MB-231 in vitro.Methods:The inhibitory effect was detected by MTT assay.Immunohistochemical assay was performed to examine the expressions of COX-2 and c-erbB-2 in SKOV3 cell line treated by NSAIDs.Results:A decrease in cell number compared with controls was observed in all of the cell line treated with ASA and Nimesulide.It was a dose-dependent inhibition of cell proliferation.COX-2 was expressed positive in MDA-MB-231 and the expression of cerbB-2 was found to decrease by immunohistochemical assay.Conclusion:NSAIDs can inhibit the growth of human breast cancer cell line MDA-MB-231 in vitro.

EFFECTS OF CYCLOOXYGENASE-2 ON ALCOHOL-INDUCED LIVER INJURY IN RATS / 解放军医学杂志

The effects of cyclooxygenase 2 (COX 2) on alcohol induced liver injury in rats were investigated. Rats were randomly divided into three groups: Control group was given with corn oil plus dextrose; Model group with corn oil plus ethanol; Treatment group with corn oil plus ethanol and a selective COX 2 inhibitor celecoxib. All materials were injected into stomach through intragastric tubes. Liver samples were analyzed with histopathology, fatty staining and immunohistochemistry. Glutathione s transferase (GST) activity of liver tissue and plasma were detected. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were measured. Compared with the control group, positive fatty staining cells and expression of COX 2 in liver, level of ALT and AST in serum and activity of GST in plasma were all significantly increased in the model group, but the GST activity in liver was decreased. However, these changes were all reversed in the treatment group. The results show that the model of alcohol induced liver injury in rats has been set up successfully, the selective COX 2 inhibitor celecoxib can protect against alcohol induced liver injury in rats and COX 2 may play a role in alcohol induced liver injury