关键词: 前列腺癌干细胞, CXCL12, CXC趋化因子受体-4, 多西紫杉醇, 蛋白激酶B

Abstract: 【Abstract】Objective To explore the expression of chemokine (C-X-C motif) receptor 4 (CXCR4) in prostate cancer stem cells (PCSCs), and the role of CXCR4 in PCSCs docetaxel resistance. Methods FACS was employed to measure the expression of CXCR4 on PCSCs and non-PCSCs surfaces; MTS was conducted to evaluate the cell viability under different concentration of docetaxel, and IC50 was calculated according to the dose-effect curves; CXCL12 or antibody against CXCR4 were used before docetaxel was added into the medium, and cell viability was measured by MTS; Western blotting was conducted to test the activation of signaling pathways. Results PCSCs cells contained 74.24% CXCR4 positive cells, while only 20.39% cells were CXCR4 positive in non-PCSCs (P<0.05); IC50 of docetaxelwas 7.5 μM in PCSCs, and 0.6 μM in non-PCSCs; 72 hours after docetaxel treatment, cell viability was 92.15±3.44% in CXCL12 group, 68.46±4.16% in anti-CXCR4 group, and 70.24±3.52% in negative control group; CXCL12 could significantly increase Akt phosphorylation in PCSCs. Conclusion CXCL12 activate the Akt signaling pathway via CXCR4 on PCSCs, inducing the docetaxel resistance of PCSCs, which may be one of the important mechanisms underlying the desensitization of docetaxel in PCSCs.

Key words: Prostate cancer stem cells, CXCL12, CXC chemokine receptor-4, Docetaxel, Protein kinase B (PKB/Akt)