Abstract:
:Toll-like receptor (TLR) signaling is an emerging pathway in tumor cell invasion and metastasis. Myeloid differentiation protein-2 (MD2) contributes to ligand recognition and activation of TLRs in response to exogenous microbial insults or endogenous agents. We hypothesized that blocking MD2 using a specific inhibitor would prevent TLR4-mediated inflammatory responses and metastatic cancer growth. Here, we report that a MD2 inhibitor, L6H21, inhibited migration and invasion of LPS-activated colon cancer CT26.WT cells. These activities were accompanied by inhibition of nuclear factor-κB (NF-κB) activation, and thereby inhibition of the production of pro-inflammatory cytokines and adhesive molecules in colon cancer cells. Furthermore, L6H21 inhibited CT26.WT metastasis to the lung in BALB/c mice as well as suppressed colitis-induced colon cancer induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Taken together, our results demonstrated that L6H21 suppressed tumor invasion and metastasis through blocking TLR4-MD2/NF-κB signaling axis. These findings reveal that inhibition of MD2 may be an important target for the development of colon cancer therapies.
journal_name
Int J Biol Scijournal_title
International journal of biological sciencesauthors
Rajamanickam V,Yan T,Xu S,Hui J,Xu X,Ren L,Liu Z,Liang G,Wang O,Wang Ydoi
10.7150/ijbs.39098subject
Has Abstractpub_date
2020-02-17 00:00:00pages
1288-1302issue
8issn
1449-2288pii
ijbsv16p1288journal_volume
16pub_type
杂志文章abstract::The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Ras(mt) alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others...
journal_title:International journal of biological sciences
pub_type: 杂志文章,评审
doi:10.7150/ijbs.15020
更新日期:2016-01-28 00:00:00
abstract::Type 2 diabetes mellitus is characterized by insulin resistance. However, the complete molecular mechanism remains unclear. In this study, zebrafish were fed a long-term high-fat diet to induce type 2 diabetes, which resulted in a higher body weight, body mass index, more lipid vacuoles in liver, increased insulin tra...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.19249
更新日期:2017-07-18 00:00:00
abstract::Lead (Pb) is a well-known neurotoxicant and a risk factor for neurologic disorders. The blood brain barrier (BBB) plays an important role in the maintenance of optimal brain function. BBB is a target of Pb, and studies have shown that Pb induced barrier loss and decreased the expression of tight junction proteins, but...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.20670
更新日期:2017-10-31 00:00:00
abstract::Our previous studies indicated that phosphoinositide specific phospholipase Cγ1 (PLCγ1) was involved in autophagy induction in colon and hepatic carcinoma cells. However, whether and how PLCγ1 regulation in human lung adenocarcinoma is linked to autophagy remains unclear. Here, we assessed the protein expression of PL...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.42962
更新日期:2020-02-21 00:00:00
abstract::Mitochondrial dysfunction is an important contributor to the development of osteoarthritis (OA). Sirtuin 3 (SIRT3) regulates diverse mitochondrial proteins to maintain mitochondrial homeostasis, and dihydromyricetin (DHM) is reported as a potential SIRT3 activator. This study aims to explore the relevance of SIRT3 and...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.27746
更新日期:2018-10-20 00:00:00
abstract::Patent ductus arteriosus (PDA) can cause morbidity and mortality in neonates. Vascular remodeling, characterized by proliferation and migration of smooth muscle cells (SMCs), is an essential process for postnatal DA closure. Notch signaling is an important mediator of vascular remodelling but its role in DA is unkonwn...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.16430
更新日期:2016-07-18 00:00:00
abstract::When pathogenic stresses are recognized by innate immune cells, inflammasomes are assembled and caspase-1 is activated, resulting in the conversion of pro-IL-18 into mature IL-18. Because natural killer (NK) cells express IL-18 receptors, IL-18 may play roles in immune functions of NK cells. In the present study, we e...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.22809
更新日期:2018-03-09 00:00:00
abstract::Lung cancer is one of the most common and deadly malignancies worldwide, in spite of advances in targeted therapy in recent years. An effective strategy for lung cancer prevention remains a major problem. Advances in next-generation sequencing have helped in understanding the RNA and identifying novel circular RNAs (c...
journal_title:International journal of biological sciences
pub_type: 杂志文章,评审
doi:10.7150/ijbs.39212
更新日期:2020-01-16 00:00:00
abstract::Solid tumors consist of various types of stromal cells in addition to cancer cells. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and play an essential role in tumor progression and metastasis in a variety of malignancies, including gastric cancer. However, the effects of CAFs on gastr...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.33750
更新日期:2019-08-22 00:00:00
abstract::Bluetongue virus (BTV) replicates in lymphoid tissues where infected mononuclear leukocytes secrete proinflammatory and vasoactive mediators that can contribute to bluetongue (BT) pathogenesis. Using the well-characterized IFNAR(-/-) mice animal model, we have now studied the histopathology and dynamics of leukocyte p...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.14967
更新日期:2016-11-24 00:00:00
abstract::Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB) which leads to infiltration of blood cells, an inflammatory response, and neuronal cell death, resulting spinal cord secondary damage. Retinoic acid (RA) has a neuroprotective effect in both ischemic brain injury and SCI, however t...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.13229
更新日期:2016-01-01 00:00:00
abstract::Melatonin is present in mammalian follicular fluid and plays an important role in regulating steroidogenesis in follicular cells. In this study, we report the effect of melatonin on steroidogenesis in the theca interna (TI) in small bovine follicles and theca cells (TCs) cultured in vitro. Treatment with melatonin sig...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.27912
更新日期:2019-01-01 00:00:00
abstract::As one of the most ominous malignancies, hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage, owing to its aggressive invasion and metastatic spread. Emerging evidence has demonstrated that Rictor, as a unique component of the mTORC2, plays a role in cell migration, as it is dysregulated in var...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.46285
更新日期:2020-09-01 00:00:00
abstract::Pathogens have developed strategies to modify Dendritic Cells (DCs) phenotypes and impair their functions in order to create a safer environment for their survival. DCs responses to helminths and their derivatives vary among different studies. Here we show that excretory/secretory products of the cestode Taenia crassi...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.7.1391
更新日期:2011-01-01 00:00:00
abstract::After spinal cord injury (SCI), the destruction of blood-spinal cord barrier (BSCB) is shown to accelerate gathering of noxious blood-derived components in the nervous system, leading to secondary neurodegenerative damages. SCI activates endoplasmic reticulum stress (ER stress), which is considered to evoke secondary ...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.21107
更新日期:2017-11-27 00:00:00
abstract::Aims: The High Mobility Group A1 (HMGA1) proteins, serving as a dynamic regulator of gene transcription and chromatin remodeling, play an influential part in the pathological process of a large number of cardiovascular diseases. However, the precise role of HMGA1 in sepsis induced cardiomyopathy (SIC) remains unintell...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.39947
更新日期:2020-03-26 00:00:00
abstract::Parkinson's disease (PD) is characterized by motor disorders and the destruction of dopaminergic neurons in the substantia nigra pars compacta. In addition to motor disability, many patients with PD present a spectrum of clinical symptoms, including cognitive decline, psychiatric alterations, loss of smell and bladder...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.42257
更新日期:2020-02-10 00:00:00
abstract::Non-coding RNAs (ncRNAs) are transcribed from genome but not translated into proteins. Many ncRNAs are key regulators of plants growth and development, metabolism and stress tolerance. In order to make the web-based ncRNA resources for plant science research be more easily accessible and understandable, we made a comp...
journal_title:International journal of biological sciences
pub_type: 杂志文章,评审
doi:10.7150/ijbs.24593
更新日期:2018-05-22 00:00:00
abstract::Breast milk is a complex liquid rich in immunological components that affect the development of the infant's immune system. Exosomes are membranous vesicles of endocytic origin that are found in various body fluids and that can mediate intercellular communication. MicroRNAs (miRNAs), a well-defined group of non-coding...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.8.118
更新日期:2012-01-01 00:00:00
abstract::Small synthetic compounds have been implicated in treatment of human cancers. We have synthesized a small compound, BPR1K0609S1 (hereafter, BP), which inhibits Aurora-A kinase. In the present study, we studied the mechanism of BP suppression of tumorigenesis induced by Aurora-A. Given our previous results that inactiv...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.5806
更新日期:2013-04-29 00:00:00
abstract::Reverting activated hepatic stellate cells (HSCs) to less activation or quiescent status is a promising strategy for liver fibrosis. Histone deacetylase inhibitor (HDACI) could suppress HSCs activation. Our previous study demonstrated a critical role of miRNAs in HSCs activation. Here, we explored the involvement of m...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.28642
更新日期:2019-01-06 00:00:00
abstract::Infectious HCV carrying reporter genes have further applications in understanding the HCV life cycle including replication, viral assembly and release. In this study, a full-length 3039bp LacZ gene was inserted into the derivative of JFH1-AM120 to develop an additional reporter virus. The results showed that the recom...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.27411
更新日期:2018-07-13 00:00:00
abstract::Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication caused by inflammation, but how it is initiated is still unclear. Several studies have shown that extracellular high mobility group box 1 (HMGB1), an important cytokine triggering inflammation, is overexpressed during the pathogenesis of S...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.50186
更新日期:2020-09-19 00:00:00
abstract::Embryonic stem (ES) cells have immortality for self-renewal and pluripotency. Differentiated human cells undergo replicative senescence. In human, the telomerase reverse transcriptase (Tert), namely the catalytic subunit of telomerase, exhibits differential expression to regulate telomerase activity governing cellular...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.7.426
更新日期:2011-04-15 00:00:00
abstract::Micro-696 (miR-696) has been previously known as an exercise related miRNA, which has a profound role in fatty acid oxidation and mitochondrial biogenesis of skeletal muscle. However, its role in skeletal myoblast proliferation and differentiation is still unclear. In this study, we found that miR-696 expressed highly...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.17508
更新日期:2017-03-11 00:00:00
abstract::Versican, a ubiquitous component of the extracellular matrix (ECM), accumulates both in tumor stroma and cancer cells and is highly regulated by various cytokines. The aberrant expression of versican and its isoforms is known to modulate cell proliferation, differentiation, and migration, all of which are features of ...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.3579
更新日期:2012-01-01 00:00:00
abstract::The objective of this work was to evaluate the bioavailability of heme iron added to biscuit filling. It comprised two stages: first, the development of the heme iron enriched biscuit filling; second, the evaluation of the bioavailability of the mineral in fattening piglets. Two groups were selected randomly and fed: ...
journal_title:International journal of biological sciences
pub_type: 杂志文章,随机对照试验
doi:10.7150/ijbs.4.58
更新日期:2008-02-18 00:00:00
abstract::RNA interference has been described as a powerful genetic tool for gene functional analysis and a promising approach for pest management. However, RNAi efficiency varies significantly among insect species due to distinct RNAi machineries. Lepidopteran insects include a large number of pests as well as model insects, s...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.10235
更新日期:2015-01-05 00:00:00
abstract::Interleukin-8 (IL-8) is a common inflammatory factor, which involves in various non-specific pathological processes of inflammation. It has been found that increased endothelial permeability accompanied with high expression of IL-8 at site of injured endothelium and atherosclerotic plaque at early stages, suggesting t...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.6996
更新日期:2013-09-23 00:00:00
abstract::Excessive inflammation induced by various risk factors is associated with the development of bronchopulmonary dysplasia (BPD). Caffeine exerts potent anti-inflammatory effects as a clinical preventive medicine for BPD. Recently, NLRP3 inflammasome activation has been demonstrated to be essential for the pathogenesis o...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.34211
更新日期:2019-06-02 00:00:00