BackgroundGlycogen synthase kinase 3 beta (GSK3β) is centrally involved in diverse cellular processes, including proliferation and apoptosis. This study aimed to investigate the influence of GSK3β expression on the prognosis of human non-small cell lung cancer (NSCLC) and the effects of GSK3β inhibition in NSCLC cell lines.MethodsImmunohistochemical and western blot assays were used to evaluate the GSK3β expression level in human NSCLC tissues. Lentiviral RNA interference was performed to inhibit the expression of GSK3β in the A549, H292, H1299 and SK-MES-1 cell lines. Cell survival, apoptosis and motility were evaluated in vivo and in vitro.ResultsThe levels of GSK3β were greater in NSCLC tissues (n = 211) than in control tissues (n = 194) (P<0.001). The 5-year follow-up analysis showed that positive GSK3β expression was indicative of poor prognosis (P = 0.006). Furthermore, knockdown of GSK3β in NSCLC cell lines suppressed cell proliferation, arrested tumor cells in G0/G1 phase, induced apoptosis and reduced cell motility. A xenograft model showed that the deregulation of GSK3β attenuated tumorigenesis, as confirmed by reduced cell proliferation based on Ki-67 and significantly increased apoptotic cell death. The inhibition of GSK3β had inconsistent effects on the expression of β-catenin, depending on the cell type examined.ConclusionAberrant expression of GSK3β serves as an independent marker of poor prognosis for NSCLC. The inhibition of GSK3β suppressed tumorigenesis by attenuating cell proliferation, increasing apoptosis and restraining cell motility. These results identify GSK3β as a tumor promoter and a potential therapeutic target in NSCLC.

Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. Currently, a lack of serological biomarkers for early LC diagnosis is a major roadblock for early intervention and prevention of LC. To undertake this challenge, we employed a two-phase strategy to discover and validate a biomarker panel using a protein array-based approach. In Phase I, we obtained serological autoimmune profiles of 80 LC patients and 20 healthy subjects on HuProt arrays, and identified 170 candidate proteins significantly associated with LC. In Phase II, we constructed a LC focused array with the 170 proteins, and profiled a large cohort, comprised of 352 LC patients, 93 healthy individuals, and 101 patients with lung benign lesions (LBL). The comparison of autoimmune profiles between the early stage LC and the combined group of healthy and LBL allowed us to identify and validate a biomarker panel of p53, HRas, and ETHE1 for diagnosis of early stage LC with 50% sensitivity at >90% specificity. Finally, the performance of this biomarker panel was confirmed in ELISA tests. In summary, this study represents one of the most comprehensive proteome-wide surveys with one of the largest (i.e. 1,101 unique samples) and most diverse (i.e. nine disease groups) cohorts, resulting in a biomarker panel with good performance.

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BackgroundBaicalin, a flavone present in Scutellaria baicalensis Georgi, inhibits the growth of human leukemia and myeloma cells through induction of apoptosis.MethodsThe present study was undertaken to ascertain whether cultured Burkitt lymphoma cells undergo apoptosis when treated with baicalin. Growth rates were measured using MTT and colony formation assays, and induction of apoptosis was quantified using Annexin V and DNA fragmentation assays. Mechanisms underlying observed growth suppression were examined using Western blotting.ResultsTreatment of CA46 Burkitt lymphoma cells with baicalin for 48 h markedly decreased the rate of cell proliferation; an IC50 value of 10 μM was obtained. Colony formation was almost fully suppressed at 10 μM baicalin. CA46 cells underwent apoptosis in response to baicalin treatment as evidenced by an increase in the percentage of cells stainable with Annexin V, by increased DNA fragmentation, and by activation of the intrinsic (mitochondrial) pathway for cell death as characterized by increased expression of the cleaved forms of caspase-9, caspase-3, and poly (ADP-ribose) polymerase. Additionally, baicalin was found to down-regulate anti-apoptotic and up-regulate apoptotic components of the phosphatidylinositide-3-kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway.ConclusionsThe concentrations at which baicalin altered expression of components of the PI3K/Akt pathway in CA46 cells were comparable to those that suppressed growth and induced apoptosis, supporting the hypothesis that the observed growth-inhibitory and apoptosis-inducing actions of baicalin in these cells are mediated by down-regulation of this pathway.