The expression of V-ATPase is associated with drug resistance and pathology of non-small-cell lung cancer

Abstract

ObjectiveThis article aims to investigate the expression of vacuolar-H + −ATPase (V-ATPase) in non-small cell lung cancer (NSCLC) and its variations with pathological type and grade. Furthermore, to evaluate the chemotherapy drug sensitivity of different cancer tissues as well as its correlation with V-ATPase expression in NSCLC.MethodsV-ATPase expression was examined in 92 NSCLC tissue samples using the immunohistochemical Envision method and immunofluorescence assay. The location of V-ATPase expression was observed by confocal laser scanning microscopy and the difference of its expression rate was evaluated. The sensitivity of cancer tissues to chemotherapy drug was examined using MTT assay and its correlation with the V-ATPase expression was tested in NSCLC by Spearman rank correlation analysis.ResultsV-ATPase expression was mainly localized in the cell membrane and cytoplasm. The expression rate of V-ATPase was 71.43% in squamous cell lung cancer, significantly lower than that of the lung adenocarcinoma (83.72%, P = 0.000). In different pathological grades of squamous cell lung cancer, the expression rate of V-ATPase was 58.33% in grade II, significantly lower than that of the grade III (84.00%, P = 0.014). The expression rate of V-ATPase in grade II lung adenocarcinoma was 76.67%, significantly lower than that of the grade ΙΙΙ adenocarcinoma (100.0%, P = 0.012). Correlation analysis showed that the sensitivity of NSCLC tissues to cyclophosphamide, gemcitabine, doxorubicin, paclitaxel and cisplatin was significantly correlated with the V-ATPase expression rate (P < 0.05).ConclusionsV-ATPase was overexpressed in NSCLC. The expression of V-ATPase was related to the pathological type and grade of cancer and was likely associated with chemotherapy drug resistance in NSCLC.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7515811511020000

Vacuolar ATPase as a potential therapeutic target and mediator of treatment resistance in cancer

“…Other studies have described expression of V‐ATPase/specific subunits in pancreatic cancer,32, 33 nonsmall cell lung cancer,34 oral squamous cell carcinoma,35, 36 ovarian cancer,37 cervical cancer,38 breast cancer,39, 40 gliomas,41 and hepatocellular carcinoma 42. A summary of studies investigating clinical significance of V‐ATPase in cancer is provided in Table 1.…”

“…Increased cancer cell invasive activity is frequently associated with aberrant V‐ATPase plasma membrane localization suggesting that increased acidification of the extracellular space plays an important role 29, 33, 34, 37, 47, 48, 49, 50, 51, 52…”

Tumor metabolism, cancer cell transporters, and microenvironmental resistance

“…It has been shown that metastatic phenotypes have higher expression of V-ATPase compared to NHE1 76 . Overexpression of V-ATPase is associated with a drug-resistant phenotype 77,78 . Weakly basic drugs such as doxorubicin are ionized extracellularly.…”

Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

“…In particular, it is overexpressed in NSCLC (Lu et al, 2013). Its expression is related to the pathological type and grade of cancer and is likely associated with chemotherapy drug resistance in NSCLC (Lu et al, 2013). Therefore, vATPase inhibitors may be promising cancer treatments.…”

“…vATPase is mainly involved in cancer metastasis and invasion (Gu and Gruenberg, 2000;Gocheva and Joyce, 2007). In particular, it is overexpressed in NSCLC (Lu et al, 2013). Its expression is related to the pathological type and grade of cancer and is likely associated with chemotherapy drug resistance in NSCLC (Lu et al, 2013).…”