Effect of celecoxib on E-cadherin, VEGF, microvessel density and apoptosis in gastric cancer

Abstract

Cyclooxygenase-2 (COX-2) plays a crucial role in the development and invasion of gastric cancer. COX-2 inhibitors have been shown to be chemopreventive against gastrointestinal cancers. In vitro studies have suggested that the mechanisms may be related to induction of apoptosis and inhibition of angiogenesis. COX-2 may also have impact on E-cadherin. In our study we investigate the effect of Celecoxib on expression of E-cadherin and serum soluble E-cadherin, as well as on apoptosis and angiogenesis in patients with gastric cancer. Fifty nine gastric cancer patients were randomly divided into two groups: Surgery group (n = 22), in which patients underwent surgical resection after diagnosis, and Celecoxib + Surgery group (n = 37), in which patients received oral Celecoxib 200 mg twice daily for 7 days before curative resection. Twenty healthy subjects (Healthy controls) were recruited as normal controls. After curative resection, COX-2, E-cadherin, VEGF, and MVD were detected by immunohistochemistry. Serum soluble E-cadherin was quantitatively measured using a commercially available enzyme-linked immunosorbent assay kit. Apoptosis was determined by TUNEL assay. Significantly decreased expression of COX-2, increased E-cadherin and apoptosis, decreased VEGF and MVD were observed in gastric cancer tissues from patients receiving Celecoxib compared to Surgery group. Compared to Healthy controls, the serum soluble E-cadherin levels were higher in gastric cancer patients which were decreased by Celecoxib. This in vivo study demonstrated that Celecoxib induces apoptosis and inhibit angiogenesis of gastric cancer. Its impact on E-cadherin may suggest that this agent may suppress the invasion of advanced gastric cancer.

Effect of celecoxib plus standard chemotherapy on serum levels of vascular endothelial growth factor and cyclooxygenase-2 in patients with gastric cancer

“…As VEGF is a potent angiogenic factor, enhancing tumor angiogenesis and contributing to tumor progression and metastasis, and COX-2 has been reported to regulate the expression and function of VEGF in cancers, the observed close correlation between the serum levels of VEGF and COX-2 indicates that blocking COX-2 may help reduce the neovascularization required for tumor growth. This observation is consistent with the findings of previous studies (17). As such, the serum levels of VEGF and COX-2 may serve as valuable biomarkers for the assessment of therapeutic benefit in gastric cancer patients receiving anticancer therapy.…”

Altered Gene Expression Profiles Define Pathways in Colorectal Cancer Cell Lines Affected by Celecoxib

“…Consistent with the effect of celecoxib on cell cycle regulation and cell death (13,15), many other celecoxibresponsive genes, such as CDC2, CDC25A, GADD45A, Figure 4. Enriched functional categories and pathways in colorectal cancer cell lines following treatment with celecoxib.…”

“…In particular, specific proteins and molecular pathways, affecting cell cycle progression and apoptosis, have been extensively studied and shown to be targeted by celecoxib (12)(13)(14)(15)(16)(17).…”

Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

“…Celecoxib in conjunction with chemotherapy reduced VEGF in mice implanted with a colon cancer cell line and also increased IFN-gamma, which is important for antitumor immunity [77]. Zhou et al reported that post-operative gastric cancer patients given celecoxib had reduced VEGF levels in cancerous tissue compared to those that received surgical intervention alone [78]. As previously mentioned, Cox-2 expression in Hodgkin's lymphoma correlated with a greater degree of angiogenesis [3].…”