Combinational chemoprevention effect of celecoxib and an oral antiangiogenic LHD4 on colorectal carcinogenesis in mice.

Abstract

To achieve a clinically rational regimen for cancer chemoprevention with improved efficacy and safety, the combination effect of celecoxib and newly developed oral angiogenesis inhibitor, LHD4, on chemoprevention was evaluated. The chemopreventive effects of celecoxib, LHD4, and the combination of celecoxib and LHD4 were evaluated in a murine colorectal carcinogenesis model. After 17 experimental weeks, mouse colon tissues were collected and examined in terms of polyp volume and degree of carcinogenesis, inflammation, and angiogenesis. Mice in the celecoxib-treated or LHD4-treated groups had total polyp volumes of 47.0±9.7 and 120.1±45.2 mm, respectively, which represented decreases of 65.6 and 22.3% from the control (154.5±33.5 mm). However, the polyp volume in the combination group was 22.8±9.3 mm, a decrease of 85.2% from the control. In the comparison of carcinogenesis, the percentage of normal tissue (i.e. excluding proliferative tissue) was found to be 40.6% in the control, 51.7% in the celecoxib, 56.9% in the LHD4, and 81.7% in the combination group. In accordance with attenuated carcinogenesis, both inflammation and angiogenesis were also well controlled. Together, these results suggest that the combinatory use of celecoxib and a newly developed oral heparin conjugate could be a promising regimen for chemoprevention by intervening in both inflammation and angiogenesis.

• Authors: Ji-young Kim, Farzana Alam, Seung Woo Chung, Jooho Park, Ok Cheol Jeon, Sang Yoon Kim, Woo Chan Son, Youngro Byun
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 25 Issue 9 Pg. 1061-71 (Oct 2014) ISSN: 1473-5741 [Electronic] England
• PMID: 25003253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Anticarcinogenic Agents
• Cyclooxygenase Inhibitors
• Heparin, Low-Molecular-Weight
• LMWH-DOCA conjugate
• Pyrazoles
• Sulfonamides
• Deoxycholic Acid
• Dextran Sulfate
• Celecoxib
• Azoxymethane

Topics

• Administration, Oral
• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Anticarcinogenic Agents (therapeutic use)
• Azoxymethane
• Carcinogenesis (chemically induced, drug effects)
• Celecoxib
• Colon (blood supply, pathology)
• Colonic Polyps (chemically induced, pathology, prevention & control)
• Colorectal Neoplasms (chemically induced, pathology, prevention & control)
• Cyclooxygenase Inhibitors (therapeutic use)
• Deoxycholic Acid (analogs & derivatives, therapeutic use)
• Dextran Sulfate
• Drug Therapy, Combination
• Heparin, Low-Molecular-Weight (analogs & derivatives, therapeutic use)
• Inflammation (chemically induced, prevention & control)
• Male
• Mice, Inbred ICR
• Neovascularization, Pathologic (chemically induced, prevention & control)
• Pyrazoles (therapeutic use)
• Sulfonamides (therapeutic use)
• Tumor Burden