Paclitaxel inhibits cell proliferation and collagen lattice contraction via TGF-β signaling pathway in human tenon's fibroblasts in vitro

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.

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