Effect of emodin on mobility signal transduction system of gallbladder smooth muscle in Guinea pig with cholelithiasis

Objective: To study the effect of emodin on protein and gene expressions of the massagers in mobility signal transduction system of cholecyst smooth muscle cells in guinea pig with cholesterol calculus. Methods: The guinea pigs were randomly divided into 4 groups, such as control group, gall-stone(GS) group, emodin group and ursodesoxycholic acid(UA) group. Cholesterol calculus models were induced in guinea pigs of GS, emodin and UA groups of induced models by lithogenic diet, while emodin or UA were given to the corresponding group for 7 weeks. The histomorphological and ultrastructure change of gallbladder were detected by microscope and electron microscope, the content of plasma cholecystokinin(CCK) and [Ca^(2+)]i were analyzed successively by radioimmunoassay and flow cytometry. The protein and mR NA of Gsα, Giα and Cap in cholecyst cells were determined by western blotting and real time polymerase chain reaction(RT-PCR). Results: Emodin or UA can relieve pathogenic changes in epithelial cells and muscle cells in gallbladder of guinea pig with cholesterol calculus by microscope and transmission electron microscope. In the cholecyst cells of GS group, CCK levels in plasma and [Ca^(2+)]i decreased, the protein and m RNA of GS group were downregulated,the protein and m RNA of Gi and Cap were up-regulated. Emodin significantly decreased the formative rate of gallstone, improved the pathogenic change in epithelial cells and muscle cells, increased CCK levels in plasma and [Ca^(2+)]i in cholecyst cells, enhanced the protein and mR NA of Gs in cholecyst cells, reduced the protein and mR NA of Gi and Cap in cholecyst cells in guinea pig with cholesterol calculus. Conclusion: The dysfunction of gallbladder contraction gives rise to the disorders of mobility signal transduction system in cholecyst smooth muscle cells, including low content of plasma CCK and [Ca^(2+)]i in cholecyst cells, abnormal protein and mRNA of Gs, Gi and Cap. Emodin can enhance the contractibility of gallbladder and alleviate cholestasis by regulating plasma CCK levels, [Ca2+]i in cholecyst cells and the protein and mR NA of Gs, Gi and Cap.

Down.regulation of E.cadherin enhances prostate cancer chemoresistance via Notch signaling

Background:The chemoresistance of prostate cancer(PCa)is invariably associated with the aggressiveness and metastasis of this disease.New emerging evidence indicates that the epithelial-to-mesenchymal transition(EMT)may play pivotal roles in the development of chemoresistance and metastasis.As a hallmark of EMT,E-cadherin is suggested to be a key marker in the development of chemoresistance.However,the molecular mechanisms underlying PCa chemoresistance remain unclear.The current study aimed to explore the association between EMT and chemoresistance in PCa as well as whether changing the expression of E-cadherin would affect PCa chemoresistance.Methods:Parental PC3 and DU145 cells and their chemoresistant PC3-Tx R and DU145-Tx R cells were analyzed.PC3-Tx R and DU145-Tx R cells were transfected with E-cadherin-expressing lentivirus to overexpress E-cadherin;PC3 and DU145 cells were transfected with small interfering RNA to silence E-cadherin.Changes of EMT phenotype-related markers and signaling pathways were assessed by Western blotting and quantitative real-time polymerase chain reaction.Tumor cell migration,invasion,and colony formation were then evaluated by wound healing,transwell,and colony formation assays,respectively.The drug sensitivity was evaluated using MTS assay.Results:Chemoresistant PC3-Tx R and DU145-Tx R cells exhibited an invasive and metastatic phenotype that associated with EMT,including the down-regulation of E-cadherin and up-regulation of Vimentin,Snail,and N-cadherin,comparing with that of parental PC3 and DU145 cells.When E-cadherin was overexpressed in PC3-Tx R and DU145-Tx R cells,the expression of Vimentin and Claudin-1 was down-regulated,and tumor cell migration and invasion were inhibited.In particular,the sensitivity to paclitaxel was reactivated in E-cadherin-overexpressing PC3-Tx R and DU145-Tx R cells.When E-cadherin expression was silenced in parental PC3 and DU145 cells,the expression of Vimentin and Snail was up-regulated,and,particularly,the sensitivity to paclitaxel was decreased.Interestingly,Notch-1 expression was up-regulated in PC3-Tx R and DU145-Tx R cells,whereas the E-cadherin expression was down-regulated in these cells comparing with their parental cells.The use ofγ-secretase inhibitor,a Notch signaling pathway inhibitor,significantly increased the sensitivity of chemoresistant cells to paclitaxel.Conclusion:The down-regulation of E-cadherin enhances PCa chemoresistance via Notch signaling,and inhibiting the Notch signaling pathway may reverse PCa chemoresistance.

Late SV40 factor:A key mediator of Notch signaling in human hepatocarcinogenesis

AIM:To investigate the relationship between late SV40 factor(LSF)and Notch signaling in the development and progress of hepatocellular carcinoma(HCC).METHODS:Liver cancer tissue specimens from 25 patients were analyzed for Notch-1 and LSF expression by immunohistochemistry.The correlation between expression and the biological effects of Notch-1 and LSF were analyzed using genetic and pharmacological strategies in HCC cell lines and human normal cell lines,including hepatic stellate cells(HSC)and human embryonic kidney epithelial cells(HEK).RESULTS:Immunohistochemistry showed that both Notch-1 and LSF were significantly upregulated in HCC samples(76%,19/25,P<0.0001 and 84%,21/25,P<0.0001,respectively)compared with non-cancer samples.Activation of Notch-1 by exogenous transfection of Notch1 intracellular domain increased LSF expression in HSC and HEK cells to levels similar to those seen in HepG2 cells.Furthermore,blocking Notch-1 activation with aγ-secretase inhibitor,DAPT,downregulated LSF expression in HepG2 cells.Additionally,a biological behavior assay showed that forced overexpression of LSF promoted HepG2 cell proliferation and invasion.CONCLUSION:LSF is a key mediator of the Notch signaling pathway,suggesting that it might be a novel therapeutic target for the treatment of HCC.

Effect of spinal cord extracts after spinal cord injury on proliferation of rat embryonic neural stem cells and Notch signal pathway in vitro

Objective:To investigate the effect of the spinal cord extracts(SCE)after spinal cord injuries(SCIs)on the proliferation of rat embryonic neural stem cells(NSCs)and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro.Methods:The experiment was conducted in 4 different mediums:NSCs+PBS(Group A-blank control group),NSCs+SCE with healthy SD rats(Croup B-normal control group),NSCs+SCE with SD rats receiving sham-operation treatment(Croup C-sham-operation group)and NSCs+SCE with SCIs rats(Group D-paraplegic group).Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1,2,3,4 and 5 d,respectively.The expressions of Notch 1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h,respectively.Results:After co-culture for 1,2,3,4 and 5 d respectively,the MTT values of group D were significantly higher than those of group A,group B and group C(P<0.05).However,there were no significantly differences regarding MTT values between group A,group B and group C after co-culture for 1,2,3,4 and 5 d,respectively(P>0.05).Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well(P<0.05).But there was no difference oin expressions of Notch1 and Hes1 mRNA among group A,group B and group C after co-culture for 24 h and 48 h(P>0.05).There was no difference in expressions of Notch1and Hes1 mRNA between 24 h and 48 h treatment in group D.Conclusions:SCE could promote the proliferation of NSCs.It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs.Besides,SCE could increase the expression of Notch1 and Hes1 mRNA of NSC.It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs.This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene.

Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury

The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 si RNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

Astrocyte-neuron communication mediated by the Notch signaling pathway:focusing on glutamate transport and synaptic plasticity

Maintaining glutamate homeostasis after hypoxic ischemia is important for synaptic function and neural cell activity,and regulation of glutamate transport between astrocyte and neuron is one of the important modalities for reducing glutamate accumulation.However,further research is needed to investigate the dynamic changes in and molecular mechanisms of glutamate transport and the effects of glutamate transport on synapses.The aim of this study was to investigate the regulatory mechanisms underlying Notch pathway mediation of glutamate transport and synaptic plasticity.In this study,Yorkshire neonatal pigs(male,age 3 days,weight 1.0–1.5 kg,n=48)were randomly divided into control(sham surgery group)and five hypoxic ischemia subgroups,according to different recovery time,which were then further subdivided into subgroups treated with dimethyl sulfoxide or a Notch pathway inhibitor(N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester).Once the model was established,immunohistochemistry,immunofluorescence staining,and western blot analyses of Notch pathway-related proteins,synaptophysin,and glutamate transporter were performed.Moreover,synapse microstructure was observed by transmission electron microscopy.At the early stage(6–12 hours after hypoxic ischemia)of hypoxic ischemic injury,expression of glutamate transporter excitatory amino acid transporter-2 and synaptophysin was downregulated,the number of synaptic vesicles was reduced,and synaptic swelling was observed;at 12–24 hours after hypoxic ischemia,the Notch pathway was activated,excitatory amino acid transporter-2 and synaptophysin expression was increased,and the number of synaptic vesicles was slightly increased.Excitatory amino acid transporter-2 and synaptophysin expression decreased after treatment with the Notch pathway inhibitor.This suggests that glutamate transport in astrocytes-neurons after hypoxic ischemic injury is regulated by the Notch pathway and affects vesicle release and synaptic plasticity through the expression of synaptophysin.

Retinal regeneration requires dynamic Notch signaling

Retinal damage in the adult zebrafish induces Müller glia reprogramming to produce neuronal progenitor cells that proliferate and differentiate into retinal neurons.Notch signaling,which is a fundamental mechanism known to drive cell-cell communication,is required to maintain Müller glia in a quiescent state in the undamaged retina,and repression of Notch signaling is necessary for Müller glia to reenter the cell cycle.The dynamic regulation of Notch signaling following retinal damage also directs proliferation and neurogenesis of the Müller glia-derived progenitor cells in a robust regeneration response.In contrast,mammalian Müller glia respond to retinal damage by entering a prolonged gliotic state that leads to additional neuronal death and permanent vision loss.Understanding the dynamic regulation of Notch signaling in the zebrafish retina may aid efforts to stimulate Müller glia reprogramming for regeneration of the diseased human retina.Recent findings identified DeltaB and Notch3 as the ligand-receptor pair that serves as the principal regulators of zebrafish Müller glia quiescence.In addition,multi-omics datasets and functional studies indicate that additional Notch receptors,ligands,and target genes regulate cell proliferation and neurogenesis during the regeneration time course.Still,our understanding of Notch signaling during retinal regeneration is limited.To fully appreciate the complex regulation of Notch signaling that is required for successful retinal regeneration,investigation of additional aspects of the pathway,such as post-translational modification of the receptors,ligand endocytosis,and interactions with other fundamental pathways is needed.Here we review various modes of Notch signaling regulation in the context of the vertebrate retina to put recent research in perspective and to identify open areas of inquiry.

Effect of the Notch signaling pathway on retinal ganglion cells and its neuroprotection in rats with acute ocular hypertension

AIM： To explore the effect of the Notch signaling pathway on retinal ganglion cells（RGCs） and optic nerve in rats with acute ocular hypertension（OH）.METHODS： Totally 48 Sprague-Dawley（SD） rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 μL phosphate buffered solution（PBS） and another group of OH rats received a single intravitreal injection of 10 μmol/L γ-secretase inhibitor（DAPT）. Quantitative real-time polymerase chain reaction（qPCR） and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43（GAP-43）. The RGC apoptosis conditions were assessed by TUNEL staining.RESULTS： The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBSinjected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat.CONCLUSION： The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.

Bevacizumab modulates retinal pigment epithelial-tomesenchymal transition via regulating Notch signaling

AIM: To investigate the effect of bevacizumab treatment on Notch signaling and the induction of epithelial-of-mesenchymal transition(EMT) in human retinal pigment epithelial cells(ARPE-19) in vitro.METHODS: In vitro cultivated ARPE-19 cells were treated with 0.25 mg/m L bevacizumab for 12, 24, and 48 h.Cell morphology changes were observed under an inverted microscope. The expression of zonula occludens-1(ZO-1), vimentin and Notch-1 intracellular domain(NICD) was examined by immunofluorescence.The m RNA levels of ZO-1, α-SMA, Notch-1, Notch-2,Notch-4, Dll4, Jagged-1, RBP-Jk and Hes-1 expression were evaluated with quantitative real-time polymerase chain reaction(q RT-PCR). The protein levels of α-SMA,NICD, Hes-1 and Dll-4 expression were examined with Western blot.RESULTS: Bevacizumab stimulation increased the expression of α-SMA and vimentin in ARPE-19 cells which changed into spindle-shaped fibroblast-like cells.Meanwhile, the m RNA expression of Hes-1 increased and the protein expression of Hes-1 and NICD also increased, which Notch signaling was activated. The m RNA expression of Notch-1, Jagged-1 and RBP-Jk increased at 48 h, and while Dll4 m RNA and protein expression did not change after bevacizumab treatment.CONCLUSION: Jagged-1/Notch-1 signaling may play a critical role in bevacizumab-induced EMT in ARPE-19 cells, which provides a novel insight into the pathogenesis of intravitreal bevacizumab-associated complication.

Protective Effect of Catalpol on Myocardium in Rats with Isoprenaline-Induced Myocardial Infarcts via Angiogenesis through Endothelial Progenitor Cells and Notch1 Signaling Pathway

Protective effect of catalpol on myocardium was studied in relation to endothelial progenitor cells, Notch1 signaling pathway and angiogenesis in rats with isoprenaline (INN)-induced acute myocardial infarcts. To analyze the pathological status and impact of catalpol on the rats, 3 weeks after intragastric gavage, the animals were verified for myocardial infarcts with electrocardiogram and measured for enzyme activity of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) and superoxide dismutase (SOD) in myocardium, and further analyzed using HE and TTC staining, as well as visual examination of infarct area. Flow cytometry study of endothelial progenitor cells (EPCs) indicated that the EPCs were mobilized during infarction. The roles of Notch1 signaling pathway in angiogenesis of the infracted animals were studied using immunohistochemistry analysis of RBPjκ and Western blot analysis of Notch1 and Jagged1. Our results obtained from the rats treated with catalpol, positive drug and control showed that catalpol could protect rats from infarction probably by mobilization of EPCs and activation of Notch1 signaling pathway.

Inhibition of Notch 1 signaling in the subacute stage after stroke promotes striatal astrocyte-derived neurogenesis

Inhibition of Notch1 signaling has been shown to promote astrocyte-derived neurogenesis after stroke.To investigate the regulatory role of Notch1 signaling in this process,in this study,we used a rat model of stroke based on middle cerebral artery occlusion and assessed the behavior of reactive astrocytes post-stroke.We used theγ-secretase inhibitor N-[N-(3,5-diuorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester(DAPT)to block Notch1 signaling at 1,4,and 7 days after injury.Our results showed that only administration of DAPT at 4 days after stroke promoted astrocyte-derived neurogenesis,as manifested by recovery of white matter fiber bundle integrity on magnetic resonance imaging,which is consistent with recovery of neurologic function.These findings suggest that inhibition of Notch1 signaling at the subacute stage post-stroke mediates neural repair by promoting astrocyte-derived neurogenesis.

Regulation of osteoprotegerin expression by Notch signaling in human oral squamous cell carcinoma cell line

Objective: To investigate the influence of Notch signaling on osteoprotegerin(OPG)expression in a human oral squamous cell carcinoma cell line.Methods: Activation of Notch signaling was performed by seeding cells on Jagged1 immobilized surfaces. In other experiments, a g-secretase inhibitor was added to the culture medium to inhibit intracellular Notch signaling. OPG m RNA and protein were determined by real-time PCR and ELISA, respectively. Finally, publicly available microarray database analysis was performed using connection up- or down-regulation expression analysis of microarrays software.Results: Jagged1-treatment of HSC-4 cells enhanced HES1 and HEY1 m RNA expression, confirming the intracellular activation of Notch signaling. OPG m RNA and protein levels were significantly suppressed upon Jagged1 treatment. Correspondingly, HSC-4 cells treated with a g-secretase inhibitor resulted in a significant reduction of HES1 and HEY1 m RNA levels, and a marked increase in OPG protein expression was observed.These results implied that Notch signaling regulated OPG expression in HSC-4 cells.However, Jagged1 did not alter OPG expression in another human oral squamous cell carcinoma cell line(HSC-5) or a human head and neck squamous cell carcinoma cell line(HN22).Conclusions: Notch signaling regulated OPG expression in an HSC-4 cell line and this mechanism could be cell line specific.

Acupuncture and moxibustion for the prevention of contrast induced nephropathy in diabetic rats by inhibiting Notch signaling pathway

Objective Apoptosis is recognized as an important mechanism in contrast-induced nephropathy(CIN).Acupuncture and moxibustion,the auxiliary treatment in China,are effective interventions for cell apoptosis in many ischemic diseases.In our previous study,we found acupuncture and moxibustion could prevent CIN.The objective of this research is to study the mechanism of acupuncture and moxibustion on tubular epithelial cell apoptosis in diabetic CIN rats.

Dysregulation of Notch signaling related genes in oral lichen planus

Objective: To investigate a dysregulation of Notch signaling in oral lichen planus(OLP)using public available microarray dataset.Methods: A m RNA expression profiling dataset from Gene Expression Omnibus was downloaded. Differential gene expression between OLP and normal oral epithelium was examined using Network Analyst. The dysregulated genes related to Notch signaling were identified.Results: Thirteen genes in Notch signaling pathway were significantly differential expressed between OLP and normal epithelium. OLP samples significantly increased the m RNA levels of HEYL, APH1 B, CNTN1 and PSEN2. Whilst, ITCH, HES1, TLE2, DLK2,DTX2, NOTCH3, JAG2, RFNG, and SPEN were downregulated in OLP groups.Conclusions: Notch signaling was dysregulated and may participate in pathophysiologic process in OLP.

Curcumin Protects SK-N-MC Cells from H₂O₂-Induced Cell Death by Modulation of Notch Signaling Pathway

Oxidative stress has been implicated to play a crucial role in the pathogenesis of Alzheimer’s disease (AD). Currently, it is known that numerous signaling pathways involved in neurodegenerative disorders are activated in response to oxidative stress. Recent directions on AD treatments have focused on the use of antioxidants including Curcumin, a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa, to augment the intracellular antioxidant defences. In the present study, hydrogen peroxide (H2O2) was used to evaluate the effects of oxidative stress on apoptotic SK-N-MC cells death with focus on changes in activity of Notch signaling pathway. The extent of lipid peroxidation, protein oxidation and intracellular ROS (Reactive Oxygen Species) levels was investigated as oxidative stress biomarkers. Here, we showed that H2O2 reduced GSH levels and activity of antioxidant enzymes and also influenced Notch signaling activation. The present data concluded that Curcumin protected cells against oxidative stress-induced apoptosis.

Role of the Notch Signaling Pathway in Fibrosis of Denervated Skeletal Muscle

In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.

Effect of Tripterine on Notch Signaling Pathway in IgA Nephropathy Rats

The objective of the study was to investigate the effect of tripterine on the Notch signaling pathway in renal tissue of IgA nephropathy rats.SD male rats were divided into the control group,IgA nephropathy model group,benazepril group,1 mg/kg/day tripterine intervention group,and 10 mg/kg/day tripterine intervention group according to the random number table method,with 10 rats in each group.The urinary sediment and 24-h urinary protein quantity were detected by conventional methods.The expressions of Notch1,Jagged1,Hes1,and Hey1 in renal tissue of rats were detected by real-time fluorescent quantitative polymerase chain reaction.IgA nephropathy model was successfully established.The hematuria and proteinuria in model group were higher than those of control group(P<0.05).The expressions of Notch1,Jagged1,Hes1,and hey1 in kidney tissue of IgA nephropathy rats were significantly increased(P<0.05).Compared with the model group,hematuria and proteinuria in the tripterine intervention group were alleviated.The expressions of Notch1,Jagged1,Hes1,and Hey1 in rat renal tissue were decreased(P<0.05).Moreover,the expressions of Notch1,Jagged1,Hes1,and Hey1 in renal tissue of rats in 10 mg/kg/day tripterine intervention group were decreased(P<0.05).Tripterine can decrease the levels of hematuria and proteinuria in IgA nephropathy rats.The expression of the Notch signaling pathway in IgA nephropathy rats is increased by the down-regulation of tripterine,suggesting that tripterine has a certain therapeutic effect on IgA nephropathy rat.Moreover,its role may be realized through this signal pathway so as to provide a new mentality for the diagnosis and treatment of IgA nephropathy.

Research progress of Notch signaling pathway and biological behavior of tumor

As an important signal transduction pathway between cells, Notch signaling pathway plays a very important role in cell recognition, proliferation, differentiation ,and apoptosis. At the same time, more and more related studies show that abnormal activation of Notch signaling pathway plays an important role in the occurrence and development of a variety of malignant tumors, and has become a hot topic in the field of tumor research. Instead of focusing on the relationship between Notch signaling pathway and various organ tumors or the relationship between Notch signaling pathway and tumor single regulatory factors, this paper focuses on the role of Notch signaling pathway by summing up and summarizing the role of the signal pathway. A series of biological behaviors of the tumor, such as angiogenesis, invasion, and metastasis, involved in Notch signaling pathway, are reviewed in this paper, as well as the recent advances in the regulation of tumor biological behavior, such as angiogenesis, invasion, metastasis and so on.

3-70 Down Regulation of Nrf2 Promotes Apoptosis through Nrf2 Mediated Notch Signaling in Non-small Cell Lung Cancer Cells

The nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant system. Nrf2 is often constitutively activated in non-small-cell lung cancer (NSCLC) cell lines, which promotes cytoprotection against oxidative stress and xenobiotics[1??3].

南瓜蛋白抑制骨髓瘤细胞系RPMI8226 Notch信号表达

本研究探讨南瓜蛋白(cucurmosin,CUS)在体外对骨髓瘤细胞RPMI8226增殖抑制的分子机制。用Western blot法检测不同浓度CUS作用骨髓瘤细胞后Notch信号通路Notch1、Jagged-2、P-Akt和NF-kB的表达水平,结果显示,CUS可以下调骨髓瘤细胞中Notch1、Jagged-2和NF-kB蛋白的表达并呈时间和浓度依赖性,同时降低BCL-2和P-Akt的表达。结论:CUS对体外培养的RPMI8226细胞具有明显的增殖抑制作用,并且能明显下调Notch信号及其下游靶基因的表达水平,因此Notch信号通路可能作为多发性骨髓瘤治疗的新靶点,而CUS也可能成为潜在的调控Notch信号通路的新药之一。