Hu Tingzhang, Yang Chun, Fu Meiling, Yang Jiali, Du Rolin, Ran Xiaolin, Yin Tieying, Wang Guixue
Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China.
Regen Biomater. 2017 Jun;4(3):167-178. doi: 10.1093/rb/rbx010. Epub 2017 May 5.
Docetaxel (DTX), a paclitaxel analogue, can efficiently inhibit proliferation of vascular smooth muscle cells and has broadly been used as an antiangiogenesis drug. However, as a candidate drug of drug-eluting stent, the effects of DTX on human umbilical vein endothelial cells (HUVECs) are still not well understood. Herein, we investigated the effects of DTX on proliferation, apoptosis, adhesion, migration and morphology of HUVECs . We found that DTX had the cytostatic and cytotoxic effects at low and high concentrations, respectively. DTX could inhibit the proliferation and migration of HUVECs, induce HUVECs apoptosis, delay HUVECs adhesion and decrease spreading area and aspect ratio of individual cells. The signaling pathway that DTX led to the migration inhibition, adhesion delay and shape change of HUVECs is the VE-cadherin mediated integrin β1/FAK/ROCK signaling pathway. The study will provide a theoretical basis for the clinical application of DTX.
多西他赛(DTX)是一种紫杉醇类似物,能有效抑制血管平滑肌细胞的增殖,已被广泛用作抗血管生成药物。然而,作为药物洗脱支架的候选药物,DTX对人脐静脉内皮细胞(HUVECs)的作用仍未完全明确。在此,我们研究了DTX对HUVECs增殖、凋亡、黏附、迁移和形态的影响。我们发现DTX在低浓度和高浓度时分别具有细胞生长抑制和细胞毒性作用。DTX可抑制HUVECs的增殖和迁移,诱导HUVECs凋亡,延迟HUVECs黏附,并减小单个细胞的铺展面积和长宽比。DTX导致HUVECs迁移抑制、黏附延迟和形态改变的信号通路是VE-钙黏蛋白介导的整合素β1/黏着斑激酶/ Rho相关卷曲螺旋蛋白激酶信号通路。该研究将为DTX的临床应用提供理论依据。