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Expression of AXL enhances docetaxel-resistance of prostate cancer cells / 中华男科学杂志
National Journal of Andrology ; (12): 302-308, 2017.
Artigo em Chinês | WPRIM | ID: wpr-812769
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.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Patologia / Farmacologia / Neoplasias da Próstata / Pirimidinas / Contagem de Células / Ciclo Celular / Proteínas Proto-Oncogênicas / Apoptose / Receptores Proteína Tirosina Quinases / Membro 1 da Subfamília B de Cassetes de Ligação de ATP Limite: Humanos / Masculino Idioma: Chinês Revista: National Journal of Andrology Ano de publicação: 2017 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Patologia / Farmacologia / Neoplasias da Próstata / Pirimidinas / Contagem de Células / Ciclo Celular / Proteínas Proto-Oncogênicas / Apoptose / Receptores Proteína Tirosina Quinases / Membro 1 da Subfamília B de Cassetes de Ligação de ATP Limite: Humanos / Masculino Idioma: Chinês Revista: National Journal of Andrology Ano de publicação: 2017 Tipo de documento: Artigo