TNF-α对非小细胞肺癌中NF-κB/PXR信号通路和去SUMO化修饰的调控作用.

Objective: To explore the regulation of TNF-α (tumor necrosis factor-alpha) on NF-κB/PXR signaling pathway and deSUMOylation modulation in non-small cell lung cancer. Methods: Human normal lung epithelial BEAS-2B cell line and human non-small cell lung cancer A549 cell line were used to investigate the changes in mRNA of NF-κB (nuclear transcription factor-κB), PXR (Pregnane X receptor), MDR-1 (multidrug resistance-1) and deSUMOylation enzymes including SENP1, SENP2, and SENP3 in recombinant human TNF-α (rhTNF-α)-induced NSCLC A549 and BEAS-2B cell line by quantitative RT-PCR (qRT-PCR). Cellular immunochemical staining was used to verify the changes in protein levels of NF-κB, PXR and SENP1. Changes of phosphorylated NF-κB were detected by Western blot. Results: The baseline expression of NF-κB mRNA was similar in both A549 cell line and control (P=0.745). Increased expression of NF-κB in mRNA and protein levels as well as phosphorylated NF-κB after TNF-α treatment was found in A549 cell line and normal control. However, the expression in A549 cells was significantly higher than BEAS-2B cells (P<0.05). The baseline expression of PXR, MDR-1 and SENP1 is higher in A549 cells, but the expression of SENP2 and SENP3 was much lower compared to BEAS-2B cells (P<0.05). The TNF-α treatment decreased the expression of PXR, MDR-1, SENP1, SENP2 and SENP3 in A549 cells, but increased the expression in BEAS-2B cells (P<0.05). Conclusions: TNF-α is involved in the contribution of NF-κB/PXR signaling pathway to carcinogenesis in NSCLC cell line. In addition, de-SUMOylation may play a role in the regulation of TNF-α on NF-κB / PXR pathway. [ABSTRACT FROM AUTHOR]