title: 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.affiliation: aResearch Institute of Pharmaceutical Sciences, College of Pharmacy bDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University cMediplex Corp. dBiomedical Research Center, Korea Institute of Science and Technology Departments of eOtolaryngology fPathology gAsan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea.
authors.forename: Ji-young
authors.initials: JY
authors.lastname: Kim
authors.forename: Farzana
authors.initials: F
authors.lastname: Alam
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Chung
authors.forename: Jooho
authors.initials: J
authors.lastname: Park
authors.forename: Ok Cheol
authors.initials: OC
authors.lastname: Jeon
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Woo Chan
authors.initials: WC
authors.lastname: Son
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects*; D000068579:Celecoxib; D003106:Colon / Q000098:blood supply / Q000473:pathology; D003111:Colonic Polyps / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016264:Dextran Sulfate; D004359:Drug Therapy, Combination; D006495:Heparin, Low-Molecular-Weight / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008813:Mice, Inbred ICR; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D016861:Cyclooxygenase Inhibitors; D006495:Heparin, Low-Molecular-Weight; C521279:LMWH-DOCA conjugate; D011720:Pyrazoles; D013449:Sulfonamides; D003840:Deoxycholic Acid; D016264:Dextran Sulfate; D000068579:Celecoxib; D001397:Azoxymethane