Effects of a Multikinase Inhibitor Motesanib (AMG 706) Alone and Combined with the Selective DuP-697 COX-2 Inhibitor on Colorectal Cancer Cells.

Abstract

In the present study, we investigated the effects of motesanib (AMG 706), a multikinase inhibitor alone and in combination with DuP-697, an irreversible selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis induction in a human colorectal cancer cell line (HT29). Real time cell analysis (RTCA, Xcelligence system) was used to determine the effects on colorectal cancer cell proliferation. Apoptosis was assessed with annexin V staining and angiogenesis was determined with chorioallantoic membrane model. We found that motesanib alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. Combination with DUP-697 increased the antiproliferative, antiangiogenic and apoptotic effects. Results of this study indicate that motesanib may be a good choice in treatment of colorectal tumors. In addition, the increased effects of combination of motesanib with DuP-697 raise the possibility of using lower doses of these drugs and therefore avoid/minimize the dose-dependent side effects generally observed.

• Authors: Tijen Temiz Kaya, Ahmet Altun, Nergiz Hacer Turgut, Hilmi Ataseven, Gokhan Koyluoglu
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 17 Issue 3 Pg. 1103-10 ( 2016) ISSN: 2476-762X [Electronic] Thailand
• PMID: 27039732 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Cyclooxygenase 2 Inhibitors
• Indoles
• Oligonucleotides
• Protein Kinase Inhibitors
• Thiophenes
• Niacinamide
• DuP 697
• Cyclooxygenase 2
• imetelstat

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chickens
• Chorioallantoic Membrane (drug effects, metabolism)
• Colorectal Neoplasms (drug therapy, metabolism)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (administration & dosage)
• HT29 Cells
• Humans
• Indoles (administration & dosage)
• Neovascularization, Pathologic (drug therapy, metabolism)
• Niacinamide (administration & dosage, analogs & derivatives)
• Oligonucleotides
• Protein Kinase Inhibitors (pharmacology)
• Thiophenes (administration & dosage)