BackgroundPlatinum-based chemotherapy is a standard strategy for non-small cell lung cancer (NSCLC), while chemoresistance remains a major therapeutic challenge in current clinical practice. Our present study was aimed to determine whether inhibition of the NF-κB/miR-21/PTEN pathway could increase the sensitivity of NSCLC to cisplatin.MethodsThe expression of miR-21 in NSCLC tissues was determined using in situ hybridization. Next, the effect of miR-21 on the sensitivity of A549 cells to cisplatin was determined in vitro. Whether miR-21 regulated PTEN expression was assessed by luciferase assay. Furthermore, whether NF-κB targeted its binding elements in the miR-21 gene promoter was determined by luciferase and ChIP assay. Finally, we measured the cell viability and apoptosis under cisplatin treatment when NF-κB was inhibited.ResultsAn elevated level of miR-21 was observed in NSCLC lung tissues and was related to a short survival time. Exogenous miR-21 promoted cell survival when exposed to cisplatin, while miR-21 inhibition could reverse this process. The RNA and protein levels of PTEN were significantly decreased by exogenous miR-21, and the 3′-untranslated region of PTEN was shown to be a target of miR-21. The expression of miR-21 was regulated by NF-κB binding to its element in the promoter, a finding that was verified by luciferase and ChIP assay. Hence, inhibition of NF-κB by RNA silencing protects cells against cisplatin via decreasing miR-21 expression.ConclusionModulation of the NF-κB/miR-21/PTEN pathway in NSCLC showed that inhibition of this pathway may increase cisplatin sensitivity.
Background Fatty acid synthase (FASN) is overexpressed in most human carcinomas, including non-small cell lung cancer (NSCLC), and contributes to poor prognosis. An increasing number of studies have highlighted the potential function of FASN as both a biomarker and therapeutic target for cancers. However, the underlying molecular mechanisms of FASN in glucose metabolism and the malignant biological behavior of NSCLC remain the subjects of intensive investigation. Methods FASN expression was depleted by FASN-siRNA in A549 and NCI-H1299 cell lines to detect the function of glucose metabolism and the malignant biological behavior of NSCLC cells. Western-blot and qPCR were applied to determine the expressions of FASN, t-AKT, p-AKT, t-ERK, p-ERK, PKM2, HK2 and AZGP1. ATP and lactate were detected to determine the activation of glucose metabolism. CCK8 and transwell assays were used to detect the proliferation, invasion, and migration capacity of the two types of NSCLC cells. The xenograft mouse model was used to evaluate tumor weights after suppression of FASN. Results LV-FASN-siRNA and its control lentiviral vector were successfully transfected into the two types of NSCLC cells (A549 and NCI-H1299). LV-FASN siRNA significantly suppressed FASN expression in both NSCLC cell types, and expressions of p-AKT, p-ERK, PKM2, and AZGP1 were also significantly decreased. Notably, the levels of ATP and lactate were significantly decreased after transfection with LV-FASN siRNA. The proliferation of both NSCLC cell types was decreased after suppression of FASN. The invasion and migration capacity of A549, but not NCI-H1299, were inhibited following down-regulation of FASN. In vivo, inhibition of FASN caused a marked animal tumor weight loss. Conclusions FASN was involved in glucose metabolism via down-regulation of the AKT/ERK pathway and eventually altered the malignant phenotype in lung cancer cells.
Background: The prognostic role of plasma fibrinogen in lung cancer remains controversial. The aim of this meta-analysis was to assess the prognostic value of plasma fibrinogen in lung cancer.Methods: We performed a systematic literature search to identify eligible studies in PubMed, Embase and the Cochrane Library database. The hazard ratios (HR) and their 95% confidence intervals (CI) were collected from these eligible studies and were used to assess the relationship between plasma fibrinogen and lung cancer.Results: A total of 16 studies including 6,881 patients were selected in this meta-analysis. The results showed that elevated plasma fibrinogen in lung cancer patients was correlated with poor overall survival (OS) (HR = 1.38, 95% CI: 1.22-1.55, P < 0.001) and disease-free survival (DFS) / progress-free survival (PFS). (HR = 1.29, 95% CI: 1.01-1.65, P = 0.042). When stratified by cut-off value for OS and DFS/PFS, there was no significant heterogeneity. And the results of “cut-off value ≥ 400mg/dl” group showed that the high level of fibrinogen in serum was associated with worse OS and DFS/PFS of lung cancer. In further subgroup analysis by tumor histology, high plasma fibrinogen was also associated with worse OS in non-small cell lung cancer (NSCLC) (HR = 1.32, 95% CI: 1.14-1.53, P < 0.001). However, there was no significant association between high plasma fibrinogen and poor DFS in NSCLC patients (HR = 1.24, 95% CI: 0.97-1.57, P = 0.08). The Egger's regression test indicated evidence of publication bias for DFS/PFS.Conclusions: Elevated plasma fibrinogen, particularly defined as a plasma fibrinogen concentration of ≥ 400mg/dl, could be a promising indicator for worse OS in lung cancer patients, including NSCLC.
The liver-X-receptors have shown anti-inflammatory ability in several animal models of respiratory disease. Our purpose is to investigate the effect of LXR ligand in allergen-induced airway remodeling in mice. Ovalbumin-sensitized mice were chronically challenged with aerosolized ovalbumin for 8 weeks. Some mice were administered a LXR agonist, T0901317 (12.5, 25, 50 mg/kg bodyweight) before challenge. Then mice were evaluated for airway inflammation, airway hyperresponsiveness and airway remodeling. T0901317 failed to attenuate the inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid. But the application of T0901317 reduced the thickness of airway smooth muscle and the collagen deposition. Meanwhile, T0901317 treatment evidently abolished the high level of OVA-specific IgE, TGF-β1 and MMP-9 in lung. So LXRs may attenuate the progressing of airway remodeling, providing a potential treatment of asthma.
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