English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

We examined the effects of the preferential cyclooxygenase-2 (COX-2) inhibitorcelecoxib on tumorigenesis, angiogenesis, apoptosis, vascular endothelial growthfactor (VEGF) protein expression and metastasis in HT-29 human colorectal carcinomacell xenografts in nude mouse rectum. COX-2 mRNA expression was examined in thexenograft and metastatic sites. The antitumor effect of celecoxib in the xenograftswas evaluated by measuring the weight of the peri-ano-rectal tumor. The anti-metastaticeffect of celecoxib was assessed by quantification of lymph node and lung metastasesby amplification of a cancer-related human DNA by TaqMan PCR. The effects of celecoxibon angiogenesis, apoptosis, prostaglandin E2 (PGE2) production and VEGF proteinexpression in the xenografts were evaluated by means of microvessel density (MVD)counting, terminal deoxynucleotidyl transferase-mediated nick end labeling assay,quantitative enzyme-linked immunosorbent assay and western blotting, respectively.The rectal xenograft model showed lymph node and lung metastases with enhancedexpression of COX-2 mRNA in each organ. Celecoxib inhibited rectal xenograft growthin a dose-dependent manner as follows: 150 ppm, 33.0% (p=0.000220); 750 ppm, 46.4%(p=0.0000292); 1500 ppm, 63.4% (p=0.0000109). Celecoxib inhibited lymph node metastasisin a dose-dependent manner as follows: 150 ppm, 86.7% (p=0.0263); 750 ppm, 90.3%(p=0.00638); 1500 ppm, 96.0% (p=0.000894). Celecoxib also inhibited lung metastasisas follows: 750 ppm, 53.3% (p=0.0107); 1500 ppm, 78.3% (p=0.00022). Celecoxib(1500 ppm) significantly inhibited PGE2 production by 68.4% (p=0.000157) and MVDcounting by 48.2% (p=1.3x10-12) and induced apoptosis 2.5-fold (p=3.0x10-14) inthe rectal xenograft. Celecoxib suppressed VEGF protein expression in the rectalxenograft. These studies demonstrate that celecoxib reduces the growth and metastaticpotential of colorectal carcinoma in mice through COX-2 inhibition, anti-angiogenesisand apoptosis induction. The studies using HT-29 human colorectal carcinoma cellxenografts in nude mouse rectum also provide important information that supportsthat the COX-2 inhibitor celecoxib has a high potential for use as a clinicalagent for inhibition of hematological and lymphatic metastases of colorectal cancer.

Antitumor and anti-metastatic effects of cyclooxygenase-2 inhibition by celecoxib on human colorectal carcinoma xenografts in nude mouse rectum