| Objective:Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme for prostaglandin (PG) synthesis from arachidonic acid. Over-expression of COX-2 has been observed in various tumors, as a new target of tumor prevention, which has a close correlation with the angiogenesis, incidence, invasion and metastasis prognosis of tumors. Vascular endothelial growth factor families, as the most important angiogenic factors so far known, have an important role on the angiogenesis of tumors, of which vascular endothelial growth factor-C (VEGF-C) is the research hotspot. The expressions of COX-2 and VEGF-C in bladder transitional cell carcinoma (BTCC) were evaluated to explore the relationships between them and the tumor biological characteristics, tumor angiogenesis and prognosis.Methods:The expressions of COX-2, VEGF-C and microvessel density (MVD) were detected by immunohistochemistry of 45 patients BTCC and 10 normal bladder urothelial epithelium tissues. The clinical information and pathological data of the patients were analyzed and a long-term follow-up was conducted.Results:(1) The positive rates of COX-2 and VEGF-C high expression in BTCC were 60.0% and 62.2%, higher than those of normal bladder urothelial epithelium tissue (P<0.05), the expression of COX-2 was corrected with the expression of VEGF-C and the R value 0.674 (P＜0.01). The value of MVD of BTCC was 49.42±10.63, higher than the value of normal bladder urothelial epithelium tissue (P<0.05). (2) The expression of COX-2 was correlated with the expression of VEGF-C and also correlated with tumor grade, TNM clinical stage, infiltration of vessels and lymphatic vessels, and lymph node metastasis, but it was not correlated with the sex and age of patients, size and number of tumor, and recurrence or no of tumor. (3) The expression of VEGF-C was correlated with the expression of COX-2 and also correlated with tumor grade, TNM clinical stage, infiltration of vessels and lymphatic vessels, and lymph node metastasis, but it was not correlated with the sex and age of patients, size and number of tumor, and recurrence or no of tumor. (4) The value of MVD was correlated with the expression of COX-2, VEGF-C, and also correlated with tumor grade, TNM clinical stage, infiltration of vessels and lymphatic vessels, and lymph node metastasis, but it was not correlated with the sex and age of patients, size and number of tumor, and recurrence or no of tumor. (5) In single factor analysis, prognosis of BTCC was correlated with the expression of COX-2, VEGF-C, and also correlated with tumor grade, TNM clinical stage, infiltration of vessels and lymphatic vessels, lymph node metastasis, and high expression of MVD of tumor, but it was not correlated with the sex and age of patients, size and number of tumor, and recurrence or no of tumor.Conclusion:The expressions of COX-2 and VEGF-C in BTCC may be related to tumor angiogenesis and prognosis. Objective:To investigate the expressions of COX-2 and VEGF-C in bladder carcinoma, to explore the relationships between them and the tumor biological characteristics, tumor lymthangiogenesis and prognosis.Methods:The expressions of COX-2, VEGF-C and lymthatic vessel density (LVD) were detected by immunohistochemistry of 45 patients with BTCC and 10 normal bladder urothelial epithelium tissues. The clinical information and pathological data of the patients were analyzed and a long-term follow-up was conducted.Results:(1) The value of peri-tumoral LVD of BTCC was 16.78±4.87, higher than the value of intra-tumoral LVD (12.00±3.91) and normal bladder urothelial epithelium tissue (6.50±1.43) (P<0.05). (2) The value of intra-tumoral and peri-tumoral LVD were correlated with the expression of COX-2, VEGF-C, and also correlated with tumor grade, TNM clinical stage, infiltration of vessels and lymphatic vessels, and lymph node metastasis, but they were not correlated with the sex and age of patients, size and number of tumor, and recurrence or no of tumor. (3) In single factor analysis, lymph node metastasis of BTCC was correlated with the expression of COX-2, VEGF-C, and also correlated with tumor grade, TNM clinical stage, infiltration of vessels and lymphatic vessels, and high expression of MVD and intra-tumoral and peri-tumoral LVD of tumor, but it was not correlated with the sex and age of patients, size and number of tumor, and recurrence or no of tumor. While in multiple-factor regression analysis, only the high expression of VEGF-C was the independent risk factor of lymph node metastasis (OR 18.462, P<0.01). (4) In single factor analysis, prognosis of BTCC was correlated with the expression of COX-2, VEGF-C, and also correlated with tumor grade, TNM clinical stage, infiltration of vessels and lymphatic vessels, lymph node metastasis, and high expression of MVD and intra-tumoral and peri-tumoral LVD of tumor, but it was not correlated with the sex and age of patients, size and number of tumor, and recurrence or no of tumor. While in multiple-factor regression analysis, only the high expression of MVD (OR 0.237, P<0.05) and lymph node metastasis (OR 0.220, P<0.05) were the independent risk factors of prognosis.Conclusion:The expressions of COX-2 and VEGF-C in BTCC may be related to tumor angiogenesis and prognosis. Objective:To investigate the effect of celebrex (celecoxib) on human bladder cancer cell line T24 implanted in nude mice in vivo, to investigate the effect of celebrex on the expression of COX-2 and VEGF-C, to study the effect of celebrex on the growth, angiogenesis and lymphangiogenesis.Methods:The transplantable human bladder carcinoma tumor models in nude mice were established and were divided into 4 groups at random 2 weeks after establishment, and treated with placebo (group C, pure water), celebrex low dose group (group L,500 ppm,0.5 mg/ml), celebrex middle dose group (group M,1000 ppm,1.0 mg/ml) and celebrex high dose group (group H,1500 ppm,1.5 mg/ml), respectively. Nude mice were sacrified at seventh week. Count the tumor inhibition rate and relative tumor proliferation rate. The expressions of COX-2, VEGF-C, MVD and LVD were deleted by immunohistochemistry, and the expressions of COX-2 mRNA and VEGF-C mRNA were deleted by semi-quantitative RT-PCR.Results:(1) No of nude mice died and the rate of tumor formation was 100 percent. The tumor volume inhibition rate of group L, group M and group H were 35.7%,45.5% and 55.1%, respectively, and the tumor weight inhibition rate were 34.5%,45.5% and 53.4%, respectively. With the increase of drug concentration, the volume and the weight of tumor decreased, the difference of different groups was significant (P<0.05 and P<0.01, respectively). (2) The relative tumor proliferation rate of group L, group M and group H were 34.5%,45.5% and 53.4%, respectively. (3) The expression of COX-2 and VEGF-C was correlated (R=0.583, P<0.01), but the difference of the expression of COX-2 and VEGF-C was not significant among 4 groups respectively. (4) MVD was correlated with the expression of COX-2 and VEGF-C, the value of MVD in high expression of COX-2 and VEGF-C was higher than that in low expression (P<0.01). With the increase of drug concentration, the level of MVD decreased, the difference of the four groups was significant (P<0.05). (5) LVD was correlated with the expression of COX-2 and VEGF-C, the value of LVD in high expression of COX-2 and VEGF-C was higher than that in low expression (P<0.01). With the increase of drug concentration, the level of LVD decreased, the difference of the four groups was significant (P<0.05). (6) Semi-quantitative RT-PCR showed that the expression of COX-2 mRNA and VEGF-C mRNA of interventional groups decreased significantly compared to control group, difference was significant except the expression of COX-2 mRNA in group L and group M. With the increase of drug concentration, the level of MVD,LVD,COX-2 mRNA and VEGF-C mRNA decreased. The level of MVD had a positive correlation with the expression of COX-2 mRNA and VEGF-C mRNA (R=0.771, R=0.865, P<0.05), and the level of LVD also had a positive correlation with the expression of COX-2 mRNA and VEGF-C mRNA (R=0.762, R=0.870, P＜0.05).Conclusion:The expression of COX-2 and VEGF-C is correlated with the angiogenesis and lymthangiogenesis of the xenograft tumor, celebrex can inhibit the growth, angiogenesis and lymthangiogenesis of the xenograft tumor as inhibiting the expression of COX-2 and VEGF-C.
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