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[Effect of TNP-470 on rat vascular smooth muscle cell growth and cell cycle]
Ying-Fang Fan1, Zong-Hai Huang, Jing Nie
1Department of General Surgery, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China.
Objective:
To study the effect of TNP-470 on the growth and cell cycle of vascular smooth muscle cells (VSMCs) in rats.
Methods:
MTT assay was employed to observe the growth inhibition of the VSMCs from rat thoracic aorta cultured in vitro by TNP-470, and the effect of TNP-470 on the cell cycle and expressions of cyclin D1, CDK4 and p27 in the VSMCs were examined by flow cytometry.
Results:
TNP-470 exhibited inhibiting effect on the growth of VSMCs in vitro, with the IC(50) value of 23.3 g/L. The cell ratios of the VSMCs at S phase and G(2)/M phase were significantly decreased to (15.43+/-5.16)% and (9.49+/-2.70)% respectively in response to TNP-470 treatment from the control levels of (22.29+/-6.80)% (P<0.05) and (16.51+/-8.61)% (P<0.05), and G(0)/G(1)-phase cell ratio significantly increased to (75.14+/-6.62)% from (60.38+/-7.23)% (P<0.001). TNP-470 had resulted in significantly lowered proliferation indexes of the VSMCs, from 39.62+/-7.23 down to 23.76+/-7.92 (P<0.001). After TNP-470 treatment, the expression of cyclin D1 and CDK4 in the VSMCs were both significantly decreased (P<0.05) while p27 underwent contrary changes (P<0.001).
Conclusion:
TNP-470 executes its inhibiting effect on VSMC growth by way of halting the cell cycles, the mechanism of which may involve the expressions of cyclin D1, CDK4 and p27.