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Liu X.,Jilin University | Pei C.,Jilin Province Peoples Hospital | Yan S.,Jilin Province Cancer Hospital | Liu G.,Jilin University | And 4 more authors.
Tumor Biology | Year: 2015

Recent evidence demonstrated an enhanced metastasis of non-small cell lung cancer (NSCLC) cells induced by lipopolysaccharide (LPS) stimulation, which reflected an important role of inflammation in tumor progression. However, the underlying mechanisms still remain unclear. Here, we evaluated the potential role of reactive oxygen species (ROS) in Toll-like receptor 4 (TLR4) signaling enhanced NSCLC metastasis. NSCLC cells were isolated from clinical surgical tissues. We found that LPS stimulation of NSCLC cells facilitates their metastasis that was accompanied by increased ROS production and could be abrogated by ROS inhibition. NADPH oxidase was essential for TLR4 signaling-enhanced NSCLC metastasis. Elevated NADPH oxidase 1 (NOX1) expression by LPS stimulation was observed. Blockade of NOX1 with ML171 alleviated enhanced NSCLC metastasis by TLR4 signaling. Enforced NOX1 expression promoted TLR4 signaling-enhanced NSCLC metastasis, while decreased NOX1 expression inhibited TLR4 signaling-enhanced NSCLC metastasis. Further, NOX1 could regulate the expression of CXCR4 and matrix metallopeptidase 9 (MMP9) in NSCLC cells. NOX1 expression in tumor tissues was correlated with TLR4 expression and clinical stages in NSCLC patients. Finally, inhibition of NOX1/ROS prevented enhanced lung tumor burdens of NSCLC by LPS-induced acute lung infection. Our findings demonstrated a crucial role of NOX1-dependent ROS for TLR4 signaling to enhance the metastasis of NSCLC, which could further the understanding of NSCLC pathogenesis and helpful for developing novel therapeutics for NSCLC. © 2015, International Society of Oncology and BioMarkers (ISOBM).

Mi C.,Yanbian University | Shi H.,Yanbian University | Ma J.,Yanbian University | Han L.Z.,Jilin Province Peoples Hospital | And 2 more authors.
Oncology Reports | Year: 2014

Celastrol is a quinone methide triterpene derived from Tripterygium wilfordii Hook F., a plant used in traditional medicine. In the present study, we reported that celastrol potentiated tumor necrosis factor-α (TNF-α)-induced apoptosis, affected activation of caspase-8, caspase-3 and PARP cleavage, and inhibited the expression of anti-apoptotic proteins such as cellular inhibitor of apoptosis protein 1 and 2 (cIAP1 and cIAP2), cellular FLICE-inhibitory protein (FLIP), and B-cell lymphoma 2 (Bcl-2). In addition, celastrol significantly reduced the invasion of MDA-MB-231 human breast cancer cells after TNF-α stimulation. As matrix metalloproteinase-9 (MMP-9) plays a critical role in tumor metastasis, we analyzed its expression with celastrol treatment. Western blot analysis and real-time PCR showed that celastrol dose-dependently suppressed TNF-α-induced MMP-9 gene expression at both the mRNA and protein levels in MDA-MB-231 cells. Taken together, our findings indicate that celastrol may be a potential candidate for breast cancer chemotherapy.

Chen J.-J.,Jilin University | Jin M.-X.,Jilin Province Peoples Hospital | Zhu S.-L.,Jilin University | Li F.,Jilin University | Ying X.,Jilin University
Bio-Medical Materials and Engineering | Year: 2014

This study aimed to establish a novel non-viral liposome vector delivering brain derived neurotrophic factor (BDNF) through the blood brain barrier. For this purpose, different water-oil ratios were tested to create liposomes for packaging the prophase synthesized plasmids encoding the BDNF proteins. In order to increase the targeted and peripheral circulation time, we connected the liposomes with transferrin (Tf) and a polyethylene glycol (PEG) long chain. The non-isotope method was used to measure the liposome envelopment ratio and ligand-binding ratio, and also to detect molecular biological features, such as particle size and stability. Tf-conjugated liposomes could be synthesized satisfactorily under the following conditions: the ratio of phospholipid to cholesterol was 1:1; the ratio of enter to plasmid was 100:1; oil phase was dichloromethane; the oil to water ratio was 4:1; the rotary evaporation temperature was 30C; the ultrasonic temperature was 10C; the ultrasonic time was 10min; and 10% trehalose was in the presence. Generated liposomes had a uniform circular shape and particle size distribution. In this experiment, we successfully established a new type of Tf-conjugated liposomes carrying the gene of BDNF and the study provides an experimental basis for the future. © 2014 - IOS Press and the authors.

Li B.,Jilin University | Li B.,University of Louisville | Liu S.,Jilin Province Peoples Hospital | Miao L.,Jilin University | Cai L.,University of Louisville
Experimental Diabetes Research | Year: 2012

Diabetic cardiomyopathy and nephropathy are two major causes of death of patients with diabetes. Extra generation of reactive oxygen species (ROS), induced by hyperglycemia, is considered as the main reason for the development of these diabetic complications. Transcription factor, NFE2-related factor 2 (Nrf2), is a master regulator of cellular detoxification response and redox status, and also provides a protective action from various oxidative stresses and damages. Recently we have demonstrated its important role in determining the susceptibility of cells or tissues to diabetes-induced oxidative stress and/or damage. Therefore, this review will specifically summarize the information available regarding the effect of Nrf2 on the diabetic complications with a focus on diabetic cardiomyopathy and nephropathy. Given the feature that Nrf2 is easily induced by several compounds, we also discussed the role of different Nrf2 activators in the prevention or therapy of various diabetic complications. These findings suggest that Nrf2 has a potential application in the clinic setting for diabetic patients in the short future. Copyright © 2012 Bing Li et al.

Lian J.-H.,Jilin University | Wang W.-H.,Jilin University | Wang J.-Q.,Jilin Province Peoples Hospital | Zhang Y.-H.,Jilin Province Peoples Hospital | Li Y.,Jilin Province Peoples Hospital
Asian Pacific Journal of Cancer Prevention | Year: 2013

Objective: MicroRNAs (miRNAs) are a small class of non-coding, single-stranded RNAs with a critical role in genesis and maintenance of renal cancer mainly through binding to 3'-untranslated regions (3'UTR) of target mRNAs, which causes a block of translation and/or mRNA degradation. The aim of the present study was to investigate the potential effects of miR-122 in human renal cell carcinomas. Methods: The expression level of miR-122 was quantified by qRT-PCR. MTT, colony formation, invasion and migration assays were used to explore the potential functions of miR-122 in human renal cell carcinoma cells. Results: Cellular growth, invasion and migration in two A498 and 786-O cells were significantly increased after miR-122 transfection. Further experiments demonstrated that overexpression of miR-122 resulted in the increase of phospho-Akt (Ser473) and phospho-mTOR (Ser2448), then activation of mTOR targets, p70S6K and 4E-BP1. Conclusions: The up-regulation of miR-122 may play an important role in the progress of renal cancer through activating PI3K/Akt signal pathway and could be a potential molecular target for anti-cancer therapeutics.

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