Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H22 murine hepatocarcinoma model

摘要: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has recently been shown to affect the development of different types cancer. The present study utilized murine H22 hepatocarcinoma model investigate molecular mechanisms involved in celecoxib-induced inhibition tumor angiogenesis. Tumor-bearing mice were randomly divided into five groups: i) control; ii) low-dose celecoxib (50 mg/kg); iii) high-dose (200 iv) 5-fluorouracil (5-FU), (20 mg/kg) and v) combination 5-FU mg/kg). antitumor effect was determined by measuring volume. Tumor angiogenesis evaluated microvessel density (MVD). histology immunostaining for CD34 endothelial cells performed detect MVD. expression levels phosphatase tensin homologue deleted from chromosome 10 (PTEN), phosphatidylinositol 3-kinase (PI3K), phospho‑Akt (P-Akt), COX-2, hypoxia-inducible factor-1α (HIF-1α) vascular growth factor-A (VEGF-A) detected ELISA, immunohistochemistry western blotting, respectively. We discovered substantial delay hepatoma as result treatment. rate induced 49.3 37.0%, respectively (P<0.05). PI3K, P-Akt, HIF-1α, VEGF-A PTEN tissues treated with demonstrated immunohistochemistry, MVD decreased dose-dependent manner Reduced PI3K P-Akt particularly apparent group ELISA blotting data showed that HIF-1α reduced increased after treatment celecoxib. In conclusion, impact may correlate reducing increasing tissue.