Abstract
Peroxiredoxin 2 (PRDX2), a member of the peroxiredoxin family of antioxidant enzymes, has been revealed to be an important player in cancer progression. However, the biological role of PRDX2 in the progression of non-small cell lung cancer (NSCLC) is poor reported. In the present study, the loss-of-function experiments were performed to investigate the specific role of PRDX2 in the growth and invasion of NSCLC. The results revealed that knockdown of PRDX2 by siRNA interference significantly suppressed the proliferation, migration, and invasion of A549 and H1299 cells, as well as diminished the activity of MMP9. Additionally, the decrease in PRDX2 expression significantly promoted apoptosis in NSCLC cells by downregulating expression of Bcl-2 and upregulating the expression of Bax, cleaved caspase 3 and cleaved caspase 9, but had no significant effect on the apoptosis of normal lung epithelial cells BEAS-2B. Moreover, PRDX2 inhibitor also inhibited the proliferation, migration, and invasion of A549 cells and promoted apoptosis. Further, our data demonstrated that silencing of PRDX2 markedly reduced the phosphorylation of Akt and mTOR and expression of downstream proteins Cyclin D1 and p70S6k. In conclusion, our findings indicate that PRDX2 exerts a prooncogenic role in the progression of NSCLC and might be a potential therapeutic target for NSCLC treatment.
Highlights
Lung cancer is the leading cause of cancer-related death in the world, with an estimated 1.8 million new cases diagnosed and 1.6 million deaths every year [1, 2]
As indicated by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis, we found that the expression of Peroxiredoxin 2 (PRDX2) mRNA was markedly upregulated in non-small cell lung cancer (NSCLC) cell lines A549 and H1299 compared to normal lung epithelial cells BEAS-2B (Figure 1(a))
These results suggest that loss of PRDX2 suppresses the proliferation of NSCLC cells in vitro
Summary
Lung cancer is the leading cause of cancer-related death in the world, with an estimated 1.8 million new cases diagnosed and 1.6 million deaths every year [1, 2]. More than 85% of the cases are non-small cell lung cancer (NSCLC), the commonest type of lung cancer, of which lung squamous cell carcinoma and lung adenocarcinoma are the most common subtypes [2,3,4]. Despite the important progress in diagnosis and treatment of NSCLC over the past two decades, the 5-year survival rate of NSCLC patients remains as low as 15% [4].
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