RESUMO
Objective: To study the relationship between sterol regulatory element binding protein-1 (SREBP-1) and nucleotide-binding oligomerization domain-like receptor protein-1 (NLRP-1) inflammasome in patients with coronary artery disease (CAD). Methods: Our research included in 3 groups: Control group, n=20 normal subjects, SAP (stable angina pectoris) group, n=49 and ACS (acute coronary syndrome) group, n=55. Plasma levels of IL-1β, IL-18 and hs-CRP were examined by ELISA, mRNA and protein expressions of SREBP-1, NLRP-1 and Caspase-1 in peripheral blood mononuclear cells (PBMC) were detected by RT-PCR and Western blot analysis. Relationships between SREBP-1 and NLRP1, Caspase-1, IL-1β, IL-18 were studied. Results: Compared with Control group, ACS group and SAP group had increased plasma levels of IL-1β, IL-18 and hs-CRP, all P<0.05; elevated mRNA and protein expressions of SREBP-1, NLRP-1 and Caspase-1 in PBMC, in addition, those expressions in ACS group was even higher than SAP group, all P<0.05. SREBP-1 level was positively related to NLRP1, Caspase-1, IL-1β and IL-18, all P<0.05. Conclusion: The expressions of SREBP-1 and NLRP1 inflammasome were increased in CAD patients; SREBP-1 and NLRP1 had positive correlation.
RESUMO
BACKGROUND: The transcription factor Forkhead box M1 (FoxM1) is known to play an important role in the development and progression of many malignancies including lung cancer. However, the relationship of FoxM1 expression and the clinical response to chemotherapy and prognosis in non-small cell lung cancer (NSCLC) remains unknown. METHODS: Total 162 NSCLC (stages IIIB and IV) patients who had tumor specimens available before treatment were assessed for FoxM1 expression using immunohistochemistry. Clinical significance was analyzed by Kaplan-Meier curves, log-rank test and multivariate Cox regression analysis. Sensitivities to cisplatin were detected by the MTT assay and drug-resistance related genes were analyzed by real-time PCR and western blot between DDP-sensitive A549 and the corresponding DDP-resistant cell subline (A549/DDP). Furthermore, small interfering RNA (siRNA) targeting FoxM1 was transfected into A549 and A549/DDP cell lines in vitro and migration and invasion were examined separately by Transwell chamber assay. RESULTS: Patients with FoxM1 expression had a significantly lower response rate (P=0.009) and poor progression-free survival (PFS, P=0.002) and overall survival (OS, P=0.007) than those without FoxM1 expression. Multivariate analyses indicated that FoxM1 positivity was an independent prognostic factor for PFS (P=0.006) and OS (P=0.021), respectively. Moreover, the expression of FoxM1 was significantly higher in A549/DDP cell subline than in A549 cells at both mRNA and protein levels. The FoxM1 inhibitor thiostrepton also showed efficacy in causing cell death and proliferative arrest in the cisplatin-resistant cells through the downregulation of FoxM1 expression. Knockdown of FoxM1 by siRNA suppressed cell migration and invasion in A549 and A549/DDP cells. Cisplatin resistance in A549/DDP cells could be partially reversed through siRNA-mediated FoxM1 inhibition. CONCLUSIONS: The expression of FoxM1 might be an independent prognostic marker for advanced NSCLC patients and FoxM1 inhibition would be a potential strategy for chemosensitization of NSCLC cells.
