title: Paclitaxel inhibits cell proliferation and collagen lattice contraction via TGF-β signaling pathway in human tenon's fibroblasts in vitro.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ninghong
authors.initials: N
authors.lastname: Chen
authors.affiliation: 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. Electronic address: dadonggene@163.com.
authors.forename: Dadong
authors.initials: D
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, No. 16369#, Jingshi Road, Jinan 250014, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan 250002, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Bi
authors.affiliation: Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan 250002, China. Electronic address: seudg2006@163.com.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Ma
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058475:Tenon Capsule / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C526317:CCN2 protein, human; D005353:Fibronectins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C574442:extra domain A fibronectin, human; D055513:Connective Tissue Growth Factor; D003094:Collagen; D017239:Paclitaxel
keywords: Collagen lattice contraction; Extra cellular matrix; Glaucoma; Human tenon's fibroblast; Paclitaxel; Transforming growth factor-β1