期刊
ONCOLOGY REPORTS
卷 34, 期 4, 页码 1726-1732出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.4155
关键词
malignant mesothelioma; NADPH oxidase; reactive oxygen species; apoptosis
类别
资金
- Aichi Cancer Center [AI 52213]
- Strategic Research Foundation Grant-Aided Project for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
- Grants-in-Aid for Scientific Research [25640107, 25460395] Funding Source: KAKEN
Malignant pleural mesothelioma (MPM) is an aggressive tumor that is characterized by dysregulated growth and resistance to apoptosis. Reactive oxygen species (ROS)-generating NADPH oxidase (Nox) family enzymes have been suggested to be involved in neoplastic proliferation. Both the antioxidant N-acetylcysteine (NAC) and the inhibitor of fiavoprotein-dependent oxidase, diphenylene iodonium (DPI), inhibited the cell viability of MPM cells in a dose-dependent manner. To examine whether Nox-mediated ROS generation confers antiapoptotic activity and thus a growth advantage to MPM cells, we analyzed the mRNA expression of Nox family members using quantitative RT-PCR in 7 MPM cell lines and a normal mesothelial cell line. Nox4 mRNA was expressed in all of the examined MPM cell lines, whereas little or no Nox2, Nox3 and Nox5 mRNA expression was detected. In 2 MPM cell lines, Nox4 mRNA expression was significantly higher than that in a normal mesothelial cell line. siRNAs targeting Nox4 suppressed ROS generation and cell viability in the MPM cell lines. In addition, DPI treatment and knockdown of Nox4 attenuated phosphorylation of AKT and ERK. Taken together, our results indicate that Nox4-mediated ROS, at least in part, transmit cell survival signals and their depletion leads to apoptosis, thus highlighting the Nox4-ROS-AKT signaling pathway as a potential therapeutic target for MPM treatment.
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