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.
Article
in En
| WPRIM
| ID: wpr-167308
Responsible library:
WPRO
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 AND METHODS: 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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Prognosis
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Protons
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Enzyme-Linked Immunosorbent Assay
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Immunohistochemistry
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Transfection
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Adenocarcinoma
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Cell Line
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Uterine Cervical Neoplasms
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Risk Factors
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Paclitaxel
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Cancer Research and Treatment
Year:
2017
Type:
Article