The proto‐oncogene MDM2 is a nuclear‐localized E3 ubiquitin ligase, which promotes tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. In this study, the anti‐infective drug nitroxoline (NXQ) was screened out to effectively inhibit cell survival of small‐cell lung cancer (SCLC) cells, and induce SCLC cell apoptosis by suppressing antiapoptotic proteins (such as Bcl‐2 and MCL1) and upregulating proapoptotic protein Bim. In the mechanistic study, NXQ was found to downregulate MDM2 expression by inducing its proteasomal degradation, and thus upregulated p53 expression, which was a substrate protein of MDM2. Moreover, overexpression of MDM2 decreased the cytotoxicity of NXQ on SCLC cells. These results demonstrated that NXQ displayed anti‐SCLC activity by suppressing MDM2 expression, which suggested that anti‐infective NXQ had potential for SCLC treatment by targeting the MDM2/p53 axis.
The aim of this study was to investigate the role of microRNA‐26b (miR‐26b) in regulating the proliferation, migration, and apoptosis of small cell lung cancer (SCLC) cells. First, we examined the expression level of miR‐26b in human normal fetal lung fibroblasts (NFLFs) and three SCLC cell lines NCI‐H466, NCI‐H1688, and NCI‐H196. In the following experiments, the three SCLC cell lines were transfected with miR‐26b mimic and inhibitor. Cell growth and survival, as well as migration and invasion capacities were determined by MTT, colony formation, Transwell migration and invasion, and wound healing assays. Cell apoptosis, production of reactive oxygen species, and mitochondrial membrane potential were also measured in the three cell lines following various treatments. As a result, we found that the level of miR‐26b was significantly lower in SCLC cells than in NFLFs. Additionally, transfection with miR‐26b mimic could inhibit proliferation, colony formation, and migration, as well as induce apoptosis in these SCLC cell lines; while miR‐26b inhibitor showed the opposite effects. Further mechanistic experiment revealed that miR‐26b could suppress the expression of myeloid cell leukemia 1 protein (Mcl‐1) and the 3′‐untranslated region (3′‐UTR) of Mcl‐1 may be the direct binding site of miR‐26b, suggesting that the effect of miR‐26b may be mediated by targeting Mcl‐1. Collectively, our findings offer a new insight into the role of miR‐26b in the pathogenesis of SCLC, and provide primary evidence supporting the potential of miR‐26b‐based therapy for the treatment of SCLC.
AIM: To investigate the clinical features, causative organisms and effects of timely vitrectomy and silicone oil tamponade without intraocular lens (IOL) removal in the treatment of acute-onset endophthalmitis after cataract surgery (APCE). METHODS: We retrospectively analyzed the clinical features and microbiological factors in 10 eyes of 10 patients with APCE at Tianjin Medical University General Hospital from January 2010 to December 2018. Data on the clinical features, causative organisms, visual acuity, intraocular pressure (IOP) and complications were collected. The mean follow-up period was 25.5mo. RESULTS: The mean age of the patients was 71.4y. The mean time between cataract surgery and the onset of endophthalmitis was 2.0d. Preoperative visual acuity ranged from no light perception to hand motion. After vitrectomy, the visual acuity increased in nine eyes (90%), and was unchanged in one eye (10%). A significant difference was observed between the mean preoperative (36.3±7.1 mm Hg) and postoperative IOP (14.9±4.3 mm Hg, P<0.05). Staphylococcus epidermidis was isolated in 5 eyes, S. aureus in 2 eyes, and Enterococcus in 1 eye. Postoperative complications mainly included fibrin exudates in the anterior chamber at the early stages in all eyes and temporary IOP elevation in one eye. No retinal detachment or ocular atrophy was observed during the follow-up period. CONCLUSION: Under systemic antibiotic treatment and timely diagnosis, vitrectomy and silicone oil tamponade without IOL removal is a safe and effective method for APCE.
Targeting nuclear factor kappa B (NF‐κB) signaling pathway has become a promising strategy for the development of new antitumor drugs. In this paper, we found that anti‐infection drug furazolidone (FZD) could significantly inhibit NF‐κB‐driven luciferase activity, and FZD could markedly inhibit both of the constitutive and tumor necrosis factor‐α (TNFα)‐triggered phosphorylation of NF‐κB p65 in small cell lung cancer (SCLC). Further studies revealed that FZD inhibited the expression of inhibitor of kappa B kinase β (IKKβ) in SCLC cells. In addition, we found that FZD had significant antitumor activities in SCLC cells. FZD could markedly suppress the cell viability of SCLC cells dose‐dependently, and FZD could significantly induce the cleavages of poly ADP‐ribose polymerase (PARP) and Caspase3, the biomarkers of cell apoptosis, in SCLC cells. The flow cytometry also revealed that FZD induced cell apoptosis in SCLC cells. Finally, we also found that overexpression of constitutively activated IKKβ could significantly abolish FZD‐induced cell growth inhibition in SCLC cells, which further confirmed that FZD displayed its anti‐SCLC activity through regulating NF‐κB signaling pathway.
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