Expression of AXL enhances docetaxel-resistance of prostate cancer cells

LIN Jian-zhong; ZHU Jia-geng; WU Hong-fei; LI Jiu-ming; DE Wei; WANG Zeng-jun

doi:10.13263/j.cnki.nja.2017.04.003

Abstract：Objective:To explore the effect of the AXL expression on the chemosensitivity of prostate cancer PC-3 and DU145cells to docetaxel and possible mechanisms.Methods:Using Western blot,we examined the expressions of the AXL protein,p-AXLand Gas6 in the docetaxel-resistant PC-3 (PC-3-DR) and DU145 (DU145-DR) cells stimulated with gradually increased concentrations of docetaxel.We transfected the PC-3 and DU145 cells with negative NC ShRNA and AXL-ShRNA,respectively,which were confirmed to be effective,detected the proliferation,apoptosis and cycle distribution of the cells by CCK8,MTT and flow cytometry after treated with the AXL-inhibitor MP470 and/or docetaxel,and determined the expression of the ABCB1 protein in the PC-3-DR and DU145-DR cells after intervention with the AXL-inhibitor R428 and/or docetaxel.Results:The expression of the AXL protein in the PC-3 and DU145 cells was significantly increased after docetaxel treatment (P ＜ 0.05).The expressions AXL and p-AXL were remarkably higher (P ＜0.05) while that of Gas6 markedly lower (P ＜0.05) in the PC-3 and DU145 than in the PC-3-DR and DU145-DR cells.The inhibitory effect of docetaxel on the proliferation and its enhancing effect on the apoptosis of the PC-3 and DU145 cells were significantly decreased at 48 hours after AXL transfection (P ＜ 0.05).MP470 obviously suppressed the growth and promoted the apoptosis of the PC-3-DR and DU145-DR cells,with a higher percentage of the cells in the G2/M phase when combined with docetaxel than used alone (P ＜ 0.05).R428 markedly reduced the expression of ABCB1 in the PC-3-DR and DU145-DR cells,even more sig nificantly in combination with docetaxel than used alone (P ＜ 0.05).Conclusion:The elevated expression of AXL enhances the docetaxel-resistance of PC-3 and DU145 prostate cancer cells and AXL intervention improves their chemosensitivity to docetaxel,which may be associated with the increased cell apoptosis in the G2/M phase and decreased expression of ABCB1.