Different growth response of rabbit's vascular endothelial and smooth muscle cells to Paclitaxel / 中国临床药理学与治疗学

ABSTRACT

AIM: To investigate the effect of paclitaxel on the quantitative growth of rabbit's vascular smooth muscle cells (SMCs) and endothelial cells (ECs) and their relationship in vitro. METHODS: An ex vivo model of endothelium repair was developed in which rabbit's SMCs were inoculated in the upper chamber and rabbit's ECs in the lower chamber of a co-culture system. 3 H-TdR incorporation and cell counting were used to determine the effect of paclitaxel on the quantitative proliferation of rabbit's vascular ECs and SMCs. The migration rate was analyzed to determine the effect of paclitaxel on the migration of rabbit's vascular ECs and SMCs. The IC50 of paclitaxel on ECs and SMCs was calculated. RESULTS: The 3 H-TdR incorporation, cell counting and migration of rabbit's vascular SMCs were inhibited by paclitaxel of 1 nmol·L-1-1 μmol·L-1 in a concentration-dependent manner (n=6, P<0.01). The 3 H-TdR incorporation and cell counting of rabbit's vascular ECs were inhibited by paclitaxel of 10 nmol·L-1-1 μmol·L-1 and migration by paclitaxel of 1 nmol·L-1-1 μmol·L-1 in a concentration-dependent manner (n=6, P<0.01). The 3 H-TdR incorporation assay resulted in the IC50 of 10.09±0.47 nmol·L-1 on SMCs and 19.06±0.35 nmol·L-1 on ECs proliferation. The migration assay resulted in the IC50 of 9.16±0.54 nmol·L-1 on SMCs and 5.37±0.51 nmol·L-1 on ECs migration. Paclitaxel (10 nmol·L-1, 20 min) inhibited SMCs growth of the confluent ECs group during the observed period. However, increased SMCs growth was observed in the proliferative ECs group 10 days after paclitaxel intervention. CONCLUSION: Paclitaxel inhibits not only SMCs but also ECs growth in rabbit's vascular. The delayed SMCs proliferation is closely related with the delayed ECs regeneration induced by paclitaxel.