Expression of AXL enhances docetaxel-resistance of prostate cancer cells.
- Author:
Jian-Zhong LIN
1
;
Jia-Geng ZHU
2
;
Hong-Fei WU
1
;
Jiu-Ming LI
1
;
Wei DE
3
;
Zeng-Jun WANG
4
Author Information
1. Department of Urology, BenQ Medical Center, Nanjing Medical University, Nanjing, Jiangsu 210019, China.
2. Department of Urology, Nanjing Hospital of Nanjing Medical University, Nanjing, Jiangsu 210006, China.
3. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
4. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
- Publication Type:Journal Article
- Keywords:
apoptosis;
cell cycle;
docetaxel;
drug resistance;
proliferation;
prostate cancer
- MeSH:
ATP Binding Cassette Transporter, Subfamily B, Member 1;
metabolism;
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
Cell Count;
Cell Cycle;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Docetaxel;
Drug Resistance, Neoplasm;
Humans;
Intercellular Signaling Peptides and Proteins;
metabolism;
Male;
Prostatic Neoplasms;
drug therapy;
metabolism;
pathology;
Proto-Oncogene Proteins;
drug effects;
genetics;
metabolism;
Pyrimidines;
pharmacology;
RNA, Small Interfering;
Receptor Protein-Tyrosine Kinases;
drug effects;
genetics;
metabolism;
Taxoids;
pharmacology
- From:
National Journal of Andrology
2017;23(4):302-308
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of the AXL expression on the chemosensitivity of prostate cancer PC-3 and DU145 cells to docetaxel and possible mechanisms.
METHODS:Using Western blot, we examined the expressions of the AXL protein, p-AXL and 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 significantly in combination with docetaxel than used alone (P <0.05).
CONCLUSIONS: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.
