[Effect of TNP-470 on rat vascular smooth muscle cell growth and cell cycle].
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).


CONCLUSIONS
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.
Fan
Ying-Fang
YF
Department of General Surgery, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China.
Huang
Zong-Hai
ZH
Nie
Jing
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000187:drug effects / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000378:metabolism; D003510:Cyclohexanes; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011518:Proto-Oncogene Proteins; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D011518:Proto-Oncogene Proteins; D012717:Sesquiterpenes; D019938:Cyclin D1; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D000077609:O-(Chloroacetylcarbamoyl)fumagillol