Chen Ninghong, Guo Dadong, Guo Yuanyuan, Sun Yuanyuan, Bi Hongsheng, Ma Xiaohua
Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, No. 48#, Yingxiongshan Road, Jinan 250002, China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, No. 48#, Yingxiongshan Road, Jinan 250002, China; Eye Institute of Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan 250002, China; Department of Ophthalmology, Yijiang District Hospital, No. 159#, Fushan Road, Wuhu 241002, China.
Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, No. 48#, Yingxiongshan Road, Jinan 250002, China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, No. 48#, Yingxiongshan Road, Jinan 250002, China; Eye Institute of Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan 250002, China.
Eur J Pharmacol. 2016 Apr 15;777:33-40. doi: 10.1016/j.ejphar.2016.02.059. Epub 2016 Feb 27.
As an anti-microtubule agent, paclitaxel has been widely applied clinically. However, the effects of paclitaxel on human tenon's fibroblast (HTF) proliferation and migration in vitro was still unclear. In the present study, we explored the influences of paclitaxel on HTF cell proliferation, cell viability, cell cycle phase distribution under various concentrations of paclitaxel (i.e., 0, 10(-8), 10(-7), 10(-6)mol/l) via real-time cell electronic system and flow cytometry, further determined the expression of TGF-β1 and connective tissue growth factor (CTGF) after treatment with different concentrations of paclitaxel. Moreover, extra cellular matrix production and collagen lattice contraction assay were also explored. The results indicate that paclitaxel could apparently inhibit the cell viability, induces the elevation of S and G2/M phases of HTFs, and downregulates the expression of both TGF-β1 and CTGF. Meanwhile, the levels of fibronectin extra domain A (EDA), collagen and collagen lattice contraction were apparently reduced after treatment with paclitaxel. Overall, paclitaxel could apparently inhibit the proliferation of HTFs and leads to cell cycle arrest at both S and G2/M phases, attenuates the generation of collagen and collagen lattice contraction, decreases the expressions of TGF-β1, CTGF and fibronectin EDA. The inhibitory mechanism of paclitaxel on HTFs is involved in TGF-β1 signaling pathway.
作为一种抗微管药物，紫杉醇已在临床上广泛应用。然而，紫杉醇对人眼Tenon囊成纤维细胞（HTF）体外增殖和迁移的影响仍不清楚。在本研究中，我们通过实时细胞电子系统和流式细胞术，探讨了不同浓度（即0、10^(-8)、10^(-7)、10^(-6)mol/L）紫杉醇对HTF细胞增殖、细胞活力、细胞周期阶段分布的影响，进一步测定了不同浓度紫杉醇处理后转化生长因子-β1（TGF-β1）和结缔组织生长因子（CTGF）的表达。此外，还探讨了细胞外基质产生和胶原凝胶收缩试验。结果表明，紫杉醇能明显抑制细胞活力，诱导HTF细胞S期和G2/M期升高，并下调TGF-β1和CTGF的表达。同时，紫杉醇处理后纤连蛋白额外结构域A（EDA）、胶原蛋白水平和胶原凝胶收缩明显降低。总体而言，紫杉醇能明显抑制HTF细胞增殖，导致细胞周期阻滞于S期和G2/M期，减弱胶原蛋白的产生和胶原凝胶收缩，降低TGF-β1、CTGF和纤连蛋白EDA的表达。紫杉醇对HTF细胞的抑制机制涉及TGF-β1信号通路。
