Proton Pump Inhibition Enhances the Cytotoxicity of Paclitaxel in Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
;
: 595-606, 2017.
Artigo
em Inglês
| WPRIM
| ID: wpr-167308
ABSTRACT
PURPOSE:
This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H⁺ ATPase (V-ATPase) in cervical cancer. MATERIALS ANDMETHODS:
The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and enzyme-linked immunosorbent assay, respectively.RESULTS:
Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (p=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (p=0.005) and overall survival (p=0.023). Co-treatment with V-ATPase siRNA or esomeprazole with paclitaxel significantly decreased the cell proliferation of cervical cancer cell lines, including HeLa and INT407, compared to cell lines treated with paclitaxel alone (p < 0.01). Moreover, V-ATPase siRNA or esomeprazole followed by paclitaxel significantly increased the expression of active caspase-3 in these cells compared to cells treated with paclitaxel alone (both, p < 0.05).CONCLUSION:
V-ATPase was predominantly expressed in cervical adenocarcinoma, and the expression of V-ATPases was associated with poor prognosis. The inhibition of V-ATPase via siRNA or PPI (esomeprazole) might enhance the chemosensitivity of paclitaxel in cervical cancer cells.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Prognóstico
/
Prótons
/
Ensaio de Imunoadsorção Enzimática
/
Imuno-Histoquímica
/
Transfecção
/
Adenocarcinoma
/
Linhagem Celular
/
Neoplasias do Colo do Útero
/
Fatores de Risco
/
Paclitaxel
Tipo de estudo:
Estudo de etiologia
/
Estudo prognóstico
/
Fatores de risco
Limite:
Humanos
Idioma:
Inglês
Revista:
Cancer Research and Treatment
Ano de publicação:
2017
Tipo de documento:
Artigo
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