科研之友
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摘要
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has recently been shown to affect the development of different types of cancer. The present study utilized a murine H-22 hepatocarcinoma model to investigate the molecular mechanisms involved in celecoxib-induced inhibition of tumor angiogenesis. Tumor-bearing mice were randomly divided into five groups: i) control; ii) low-dose celecoxib (50 mg/kg); iii) high-dose celecoxib (200 mg/kg); iv) 5-fluorouracil (5-FU), (20 mg/kg) and v) combination of 5-FU and celecoxib (50 mg/kg). The antitumor effect of celecoxib was determined by measuring tumor volume. Tumor angiogenesis was evaluated by microvessel density (MVD). Tumor histology and immunostaining for CD34 in endothelial cells were performed to detect MVD. The expression levels of phosphatase and tensin homologue deleted from chromosome 10 (PTEN), phosphatidylinositol 3-kinase (PI3K), phospho-Akt (P-Akt), COX-2, hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor-A (VEGF-A) were detected by ELISA, immunohistochemistry and western blotting, respectively. We discovered substantial growth delay in murine H-22 hepatoma as a result of celecoxib treatment. The inhibition rate of tumor growth induced by high-dose and low-dose celecoxib was 49.3 and 37.0%, respectively (P<0.05). The expression of PI3K, P-Akt, COX-2, HIF-1 alpha, VEGF-A and PTEN in tumor tissues treated with celecoxib was demonstrated by immunohistochemistry, and the MVD was decreased in a dose-dependent manner (P<0.05). Reduced PI3K and P-Akt was particularly apparent in the high-dose celecoxib group (P<0.05). ELISA and western blotting data showed that the expression of PI3K, P-Akt, COX-2, HIF-1 alpha and VEGF-A were reduced and PTEN was increased after treatment with celecoxib. In conclusion, the impact of celecoxib-induced tumor growth delay of murine H-22 hepatocarcinoma may correlate with the inhibition of angiogenesis by reducing PI3K, P-Akt, COX-2, HIF-1 alpha and VEGF-A expression and increasing PTEN expression in tumor tissue.
