Effects of caffeic acid phenethyl ester on proliferation of vascular smooth muscle cells in rats

Objective: To investigate the inhibitory effect of caffeic acid phenethyl ester(CAPE) on the proliferation of vascular smooth muscle cells (VSMC) activated by lipopolysaccharide (LPS) and to clarify its mechanism. Methods: VSMC activated by LPS(1 mg·L-1) were treated with CAPE at different concentrations. The inhibitory effects of CAPE on the proliferation of VSMC were determined by methabenzthiazuron(MTT) colorimetry. The effects of CAPE on the expression of proliferating cell nuclear antigen(PCNA) and Survivin protein in VSMC were evaluated by immunocytochemistry staining technique(SABC method). Cell cycle was analyzed by flow cytometry(FCM) with propidium iodide (PI) labeling method. The relative expression level of Survivin mRNA was measured with real-time quantified RT-PCR technique. Results: CAPE exerted significant inhibitory effects on proliferation of VSMC at concentrations ranging from 5 mg·L-1 to 80 mg·L-1, decreased the rate of cells positive for PCNA and Survivin protein and repressed the expression of Survivin mRNA in a dose- and time-dependent manner(P < 0.05). FCM analysis displayed that CAPE up-regulated the ratio of G0/G1 stages and reduced the percentage of VSMC in S stage(P < 0.05). Conclusion: CAPE can significantly inhibit the proliferation of VSMC activated by LPS in a dose- and time-dependent manner, which may be carried out through regulating cell cycle and repressing the expression of PCNA and Survivin.