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Interferon-γ Upregulates SOCS3 Expression to Reduce Cisplatin Chemoresistance in Non-Small Cell Lung Cancer A549 Cells

Xu Y, Tang H, Gong L, Hu H, Chen L, Sui X, Xia D and Pan H

Abstract Background: Cisplatin (DDP)-based chemotherapy is the mainstay of first-line therapeutic strategy for the treatment of advanced non-small cell carcinoma (NSCLC). However, the anticancer efficacy of DDP is often limited by the existence or development of chemoresistance. Thus, we investigated the effect of interferon-γ on DDPresistant A549 cell. Methods: Semi-quantitative RT–PCR was used to compare the differences of SOCS3 mRNA expression in both cisplatin-resistant A549 (A549/DDP) cell and the parental A549 cell. The cellular sensitivity to cisplatin, cell viability and apoptosis were detected by MTT, flow cytometry and Western blotting. Results: Semi-quantitative RT–PCR and western blotting showed that SOCS 3 expression was significantly down-regulated in A549/DDP cell compared to the parental A549 and normal human bronchial epithelial cells BEAS-2B. IFN-γ treatment could restore SOCS3 expression, resulting in an increased sensitivity of these resistant A549 cells to DDP. In addition, p53 and Bcl-2 signaling pathways were also involved in regulating IFN-γ-induced cell death in DDP-resistant A549 cells. Conclusion: Our study indicates that SOCS 3 may play a crucial role in the progress of cisplatin resistance of A549. Moreover, IFN-γ could induce SOCS3 expression and potentiate the re-sensitization of these resistant A549 cells to DDP