INHIBITORY EFFECT OF COLCHICINE ON VASCULAR SMOOTH MUSCLE CELL PROLIFERATION INDUCED BY PLATELET-DERIVED GROWTH FACTOR-BB

Sook Nam Park, MS, Man Kyu Huh, PhD and Yong Lim*, PhD

ABSTRACT

Abnormal proliferation of rat aortic vascular smooth muscle cells (VSMCs) is thought to play an important role in the pathogenesis of atherosclerosis and restenosis. The aim of this study was to elucidate the antiproliferative effects and molecular mechanism of colchicine on platelet-derived growth factor (PDGF)-BB-stimulated rat aortic vascular smooth muscle cells (VSMCs). Antiproliferative effects of colchicine on rat aortic VSMCs were examined by direct cell counting and by using [3H] thymidine incorporation assays. It was found that colchicine potently the growth of VSMCs. Pre-incubation with colchicine (0.1∼10 μM) significantly inhibited proliferation. In accordance with these findings, colchicine blocked the PDGF-BB induced progression of synchronized cells through the G0/G1 phase of the cell cycle. Whereas, colchicine did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by CCK-8 assay. Colchicine inhibited the PDGF-BB-stimulated phosphorylation of p38. Colchicine also inhibited the proliferating cell nuclear antigen (PCNA), a key regulator in the cell cycle. These findings suggest that the inhibition of colchicine to the cell proliferation. In conclusion, colchicine may be a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

Keywords: Antiproliferative effects, Colchicine, Platelet-derived growth factor (PDGF)-BB, Vascular smooth muscle cells (VSMCs).