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Original Article
- Proton Pump Inhibition Enhances the Cytotoxicity of Paclitaxel in Cervical Cancer
- Taejong Song, Hye-Kyung Jeon, Ji Eun Hong, Jung-Joo Choi, Tae-Joong Kim, Chel Hun Choi, Duk-Soo Bae, Byoung-Gie Kim, Jeong-Won Lee
- Cancer Res Treat. 2017;49(3):595-606. Published online September 27, 2016
- DOI: https://doi.org/10.4143/crt.2016.034
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Abstract
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Supplementary Material
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ePub - 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. -
Citations
Citations to this article as recorded by
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- Pathways to precision medicine in cervical cancer: a comprehensive review of small molecule inhibitors, biomarkers and computational approaches
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