5-Fluorouracil Inhibits Proliferation of Bone Marrow Stromal Cells via Down-Regulating Wnt/β-catenin Signaling Pathway
Xiao Hanxianzhi, Qi Rongjia, Wang Ziling, Xiao Minghe, Cheng Xiao,WangYaping, Wang Lu*
This article was to explore the possible mechanism of 5-fluorouracil (5-FU) inhibiting the proliferation of human bone marrow stromal cells (HS-5), and to find a therapeutic target for improving the hematopoietic damage of chemotherapy drugs. HS-5 cells were divided into three groups. The control group was routinely cultured; the 5-FU group was treated by 5-FU on the concentration of 25 μg/mL; the LiCl+5-FU group was pretreated with LiCl on the concentration of 10 mmol/L, and 25 μg/mL 5-FU was added after 6 h, each group was cultured for 48 h. The proliferation of HS-5 cells was detected by EdU. The cell cycle was analyzed by flow cytometry. The expressions of β-catenin, CyclinD1, and C-myc proteins were measured by Western blot. The levels of reactive oxygen species (ROS) in cells were detected by DCFH-DA fluorescence. The expression of Cx43 protein was measured by Western blot. Compared with the control group, the proliferative capacity of HS-5 cells decreased, the cell cycle was blocked, intracellular ROS level was significantly increased, and the expressions of β-catenin, CyclinD1, C-myc, and Cx43 proteins were down-regulated in the 5-FU group. Compared with the 5-FU group, the proliferation of HS-5 cells in the LiCl+5-FU group was increased, the cell cycle arrest was attenuated, intracellular ROS level was decreased, and the expressions of β-catenin, CyclinD1, C-myc and Cx43 proteins were up-regulated. 5-FU can inhibit the proliferation of HS-5 cells by the mechanism of down-regulating Wnt/β-catenin signaling pathway, which may lead to 5-FU-induced oxidative stress and down-regulation of Cx43 expression.
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