Na,K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer
ABSTRACT Diminished Na,K-ATPase expression has been reported in several carcinomas and has been linked to tumor progression. However, few studies have determined whether Na,K-ATPase function and expression are altered in lung malignancies. Because cigarette smoke (CS) is a major factor underlying lung carcinogenesis and progression, we investigated whether CS affects Na,K-ATPase activity and expression in lung cell lines. Cells exposed to CS in vitro showed a reduction of Na,K-ATPase activity. We detected the presence of reactive oxygen species (ROS) in cells exposed to CS before Na,K-ATPase inhibition, and neutralization of ROS restored Na,K-ATPase activity. We further determined whether Na,K-ATPase expression correlated with increasing grades of lung adenocarcinoma and survival of patients with smoking history. Immunohistochemical analysis of lung adenocarcinoma tissues revealed reduced Na,K-ATPase expression with increasing tumor grade. Using tissue microarray containing lung adenocarcinomas of patients with known smoking status, we found that high expression of Na,K-ATPase correlated with better survival. For the first time, these data demonstrate that CS is associated with loss of Na,K-ATPase function and expression in lung carcinogenesis, which might contribute to disease progression.
- Lung Cancer 06/2012; 77:S8–S9. DOI:10.1016/j.lungcan.2012.05.015 · 3.74 Impact Factor
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ABSTRACT: Aim: The present study evaluated the expression of α1 and β1 Na,K-ATPase, as well as the effects of digoxin (DGX) on oral squamous cell carcinomas (OSCCs). Patients and Methods: Immunohistochemical expression of α1 and β1 Na,K-ATPase were evaluated in 60 patients who underwent treatment at the São João de Deus Hospital. SCC-25 viability was assessed by the colorimetric assay. Chi-square or Fisher’s exact tests were used to analyze the association of α1 and β1 Na,K-ATPase expression with the variables. Results: Immunoexpression of α1 and β1 Na,K-ATPase were observed in 28% and 55% of the tumors, however these proteins were not significant prognostic factors. Tobacco was significantly associated with α1 expression. SCC-25 viability decreased significantly after treatment with 1 μM DGX at 24 h. Conclusion: The smoking status of OSCC patients was significantly associated with α1 expression and DGX affected the SCC-25 viability in a dose- and duration-dependent mannerAnticancer research 10/2014; 34:5397- 5404. · 1.87 Impact Factor
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ABSTRACT: Tobacco use is an established risk factor for the development of several cancers; however, far less work has been done to understand the effects of continued smoking on cancer treatment outcomes, and structured tobacco cessation efforts are not well incorporated into the standard care for patients with cancer. In this Review we discuss the known biological effects of smoking on cancer cell biology and emphasise the clinical effects of continued smoking in patients with cancer treated with chemotherapy or radiotherapy. Although evidence supports the need for inclusion of dedicated tobacco cessation efforts for patients with cancer, clinicians should consider the methods used to provide evidence-based tobacco cessation support and the available resources to deliver and maintain consistent tobacco cessation support. We also address the variables to consider in the design and implementation of a sustainable tobacco cessation programme. Copyright © 2014 Elsevier Ltd. All rights reserved.The Lancet Oncology 11/2014; 15(12):e568-e580. DOI:10.1016/S1470-2045(14)70266-9 · 24.73 Impact Factor