1.Effects of As2O3 and all-trans retinoic acid on the growth of HeLa cell line and their relation with gene NDRG1.
Xiao-Xing GENG ; Li-Na QUAN ; Rong MA ; Li-Ping TANG
Chinese Journal of Oncology 2011;33(1):8-12
OBJECTIVETo study the effect of arsenic trioxide (As2O3) and all-trans retinoic acid (ATRA) on human cervical carcinoma HeLa cell line.
METHODSHeLa cells were treated with As2O3 and ATRA. The cell proliferation was evaluated by MTT assay. The expressions of NDRG-1 protein and mRNA were determined by Western blot and RT-PCR analysis.
RESULTSMTT assay showed that As2O3 and ATRA inhibited the growth of human cervical carcinoma HeLa cells in vitro in a dose- and time-dependent manner. Western blot and RT-PCR techniques showed that As2O3 and ATRA down-regulated the expressions of NDRG-1 protein and mRNA (P < 0.05).
CONCLUSIONAs2O3 and ATRA can significantly inhibit the growth and proliferation of HeLa cells. The reason of these changes may be related with the down-regulation of expression of NDRG-1.
Antineoplastic Agents ; administration & dosage ; pharmacology ; Arsenicals ; administration & dosage ; pharmacology ; Blotting, Western ; Cell Cycle Proteins ; genetics ; metabolism ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Oxides ; administration & dosage ; pharmacology ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tretinoin ; administration & dosage ; pharmacology
2.Protective effect of Shouwu Yizhi decoction against vascular dementia by promoting angiogenesis.
Xiao-Ni YANG ; Chang-Sheng LI ; Chao CHEN ; Xiao-Yong TANG ; Guang-Qing CHENG ; Xia LI
Chinese Journal of Natural Medicines (English Ed.) 2017;15(10):740-750
Shouwu is a traditional Chinese medicine (TCM) with neuroprotective effect. Shouwu Yizhi decoction (SYD) was designed based on TCM theory. However, little is known about the roles of SYD in Vascular dementia (VaD). The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion (I/R) rat model to induce VaD. SYD administration (54 mg·kg) for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion (MCAO) rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test. Moreover, SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats, thereby alleviating VaD. Mechanistically, SYD caused increases in the expression of vascular endothelial growth factor (VEGF), CD34 and CD31, compared with the MCAO rats in coronal hippocampus. Simultaneously, the expression level of miR-210 was elevated significantly after SYD administration, compared with the vehicle rats (P < 0.01). The expression of Notch 4 at both mRNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats (P < 0.05). Overall, the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced miR210 expression to activate Notch pathway, and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats, ultimately enhancing the cognition and memory of MCAO rats. Therefore, our findings preliminarily identified the effect and the mechanism of action for SYD on VaD in rats. SYD could be a potential candidate in treatment of VaD.
Angiogenesis Inducing Agents
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administration & dosage
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Animals
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Dementia, Vascular
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drug therapy
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genetics
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metabolism
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psychology
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Drugs, Chinese Herbal
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administration & dosage
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Humans
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Intracellular Signaling Peptides and Proteins
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genetics
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metabolism
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Male
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Membrane Proteins
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genetics
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metabolism
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Memory
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drug effects
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Neuroprotective Agents
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administration & dosage
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Rats
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Rats, Wistar
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Receptor, Notch4
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genetics
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metabolism
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Vascular Endothelial Growth Factor A
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genetics
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metabolism
3.Effects of azidothymidine on p33ING1b expression, apoptosis and senescence of TJ905 human glioblastoma cell line.
Qian WANG ; Shi-zhu YU ; Wen-juan ZHAO ; Jing LIU ; Cui-yun SUN ; Tong-ling AN ; Li-li WANG ; Xiao-li REN ; Xiu-ju CHEN
Chinese Journal of Pathology 2010;39(10):686-690
OBJECTIVESTo investigate the pharmacological effects of azidothymidine (AZT) on p33ING1b expression, senescence and apoptosis of TJ905 glioblastoma cells.
METHODSTJ905 cells were treated with AZT at a serial concentrations of 50, 100 and 200 µmol/L. Semi-quantitative RT-PCR and cytochemical staining of senescence related-galactosidase (sβ-Gal) were used to evaluate the expression of p33ING1b mRNA and to label the senescent cells at the 1st, 3rd and 6th generations, respectively. In situ cell death detection and single cell gel electrophoresis were used to detect the apoptosis at the 3rd and 6th generations.
RESULTSAZT induced the expression of p33ING1b mRNA and senescence of the tumor cells of the 1st generation in a dosage and time dependent manner. At the 6th generation, the relative amount of p33ING1b RT-PCR product (1.44±0.23) and sβ-Gal labeling index of 200 µmol/L group (45.62±6.74) were significantly higher than those of the 1st (0.95±0.13 and 7.82±2.40) and the 3rd generation cells (1.35±0.23, 26.27±7.17) of the same group, and cells of the same generation in the 50 µmol/L (0.85±0.24, 27.37±6.41) and 100 µmol/L groups (1.23±0.34, 35.49±5.12, P<0.01). There was a significant positive correlation between the p33ING1b mRNA expression and the labeling index of sβ-Gal. Pro-apoptotic effects of AZT became obvious at the 6th generation.
CONCLUSIONAZT upregulates the expression of p33ING1b, a possible mechanism in regulating senescence and apoptosis of the TJ905 cells.
Apoptosis ; drug effects ; Brain Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cellular Senescence ; drug effects ; Dose-Response Relationship, Drug ; Glioblastoma ; metabolism ; pathology ; Humans ; Inhibitor of Growth Protein 1 ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Nuclear Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Reverse Transcriptase Inhibitors ; administration & dosage ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Proteins ; genetics ; metabolism ; Zidovudine ; administration & dosage ; pharmacology
4.Effect of ACBP-S on cell cycle and apoptosis in human gastric cancer cells.
Xiu-lan SU ; Xiao-hui OUYANG ; Gui-hua XU ; Jie SHEN ; Zhao-yang WANG
Chinese Journal of Oncology 2008;30(6):422-427
OBJECTIVETo explore the impact of anti-cancer bioactive peptide-S (ACBP-S) on cell proliferation, cell cycle and apoptosis in human stomach cancer cell line MGC-803 cells.
METHODS(1) The cultured MGC-803 cells were treated with ACBP-S at various concentrations for 24, 48, 72 h, respectively. The inhibition rate of proliferation of MGC-803 cells were evaluated by MTT assay. Cell apoptosis was observed by transmission electron microscopy. Cell cycle and apoptosis were analyzed by flow cytometry (FCM). RT-PCR was used to assay the changes of p27 mRNA expression. Immunocytochemistry was used to detect the changes of expression of p27, PCNA, Bax, Bcl-2 proteins, respectively. (2) a nude mouse xenograft model with gastric carcinoma cell was established. ACPB-S was administered into the tail vein of the mice in a dose of 7 microg, every other day, and the mice were killed after two weeks. The tumors were taken off for further analysis.
RESULTS(1) ACBP-S at concentrations of 5.0, 10.0 and 15.0 microg/ml inhibit the growth of MGC-803 cells in a concentration- and time-dependent manner. The concentration of ACBP-S at 20.0 microg/ml showed an inhibition rate of (86.6 + 0.1)%. Typical apoptotic changes were observed under the transmission electron microscope. The result of FCM in the range of 5.0 and 20.0 microg/ml for 24 h showed higher early apoptosis rates, (5.7 +/- 0.2)% and (13.9 +/- 0.6)%, respectively, with s significant difference compared with that of the control group (P < 0.05). The ratio of G0/G1 was significantly increased with the increase of incubation time at 20 microg/ml. RT-PCR showed that the expression of p27 mRNA in MGC-803 cells was markedly increased after ACBP-S treatment. (2) After ACBP-S administration the tumor growth in nude mice was inhibited by 34.2%. More apoptotic and necrotic cells were observed in the mice of treatment group by histological examination with HE staining. The immunocytochemistry demonstrated that the expression of Bax protein was significantly increased and Bcl-2 and PCNA protein expressions were significantly decreased after ACBP-S treatment.
CONCLUSIONACBP-S has marked inhibiting effect upon the growth of MGC-803 cells inducing more apoptosis. The anti-cancer mechanism is probably related with its regulatory effects on cell cycle and apoptosis in the tumor cells.
Animals ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p27 ; Dose-Response Relationship, Drug ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Peptides ; administration & dosage ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; bcl-2-Associated X Protein ; metabolism
5.The mechanism of JWA gene involved in oxidative stress of cells.
Nan-ping WANG ; Jian-wei ZHOU ; Ai-ping LI ; Hai-xia CAO ; Xin-ru WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2003;21(3):212-215
OBJECTIVETo study the mechanism of gene JWA involved in oxidative stress under hydrogen peroxide (H(2)O(2)) exposure.
METHODSBoth MCF-7 (human breast cancer cell line) and WI-38 (human embryo lung fibroblast cell line) cells were treated with 1 mmol/L of H(2)O(2) with or without pre-incubation of taurine (tau). Malondialdehyde (MDA) and glutathione (GSH) contents in supernatant of cell culture were measured; RT-PCR and Western blotting were carried out for evaluation of the expressions of JWA mRNA and protein respectively. Heat shock proteins (HSP27, HSP70 and HSP90) were also analyzed.
RESULTSThe contents of MDA before and after H(2)O(2) treatment in MCF-7 cells were (0.531 +/- 0.038), (0.674 +/- 0.410) mmol/L respectively, (P < 0.01), while those in WI-38 cells were (0.572 +/- 0.035), (0.683 +/- 0.028) mmol/L respectively, (P < 0.01). The contents of GSH before and after H(2)O(2) treatment in MCF-7 cells were (0.053 +/- 0.002), (0.044 +/- 0.002) g/L respectively, (P < 0.01), while those in WI-38 cells were (0.058 +/- 0.002), (0.050 +/- 0.002) g/L respectively, (P < 0.01). The expression of JWA mRNA was down regulated, at 6 h it decreased by 68.4%, while in WI-38 cells no obvious change found. JWA protein and HSP27 showed markedly increased after H(2)O(2) treatment in both cells but not in similar extent.
CONCLUSIONOxidative stress signal pathways of JWA gene varied between cancer and non-cancer cell lines; JWA protein may have a similar function as HSP27 and act as an important signal molecule in H(2)O(2) induced cell injury.
Blotting, Northern ; Cell Line ; Cell Line, Tumor ; Gene Expression Regulation ; drug effects ; Glutathione ; metabolism ; HSP70 Heat-Shock Proteins ; metabolism ; HSP90 Heat-Shock Proteins ; metabolism ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Hydrogen Peroxide ; administration & dosage ; Intracellular Signaling Peptides and Proteins ; Malondialdehyde ; metabolism ; Oxidative Stress ; RNA, Messenger ; drug effects ; genetics ; metabolism
6.Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.
Hoon Jae JEONG ; Dae Won KIM ; Mi Jin KIM ; Su Jung WOO ; Hye Ri KIM ; So Mi KIM ; Hyo Sang JO ; Hyun Sook HWANG ; Duk Soo KIM ; Sung Woo CHO ; Moo Ho WON ; Kyu Hyung HAN ; Jinseu PARK ; Won Sik EUM ; Soo Young CHOI
Experimental & Molecular Medicine 2012;44(10):586-593
Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.
Animals
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Blood-Brain Barrier/metabolism
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Brain Ischemia/*metabolism/pathology/prevention & control
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CA1 Region, Hippocampal/drug effects/metabolism/pathology
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Cell Line, Tumor
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Cell Survival/drug effects
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Gerbillinae
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Intracellular Signaling Peptides and Proteins/*administration & dosage/biosynthesis/pharmacokinetics
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Lipid Peroxidation
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Malondialdehyde/metabolism
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Mice
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Neuroprotective Agents/*administration & dosage/pharmacokinetics
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Oncogene Proteins/*administration & dosage/biosynthesis/pharmacokinetics
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*Oxidative Stress
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Prosencephalon/drug effects/metabolism/pathology
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Rats
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Recombinant Fusion Proteins/*administration & dosage/biosynthesis/pharmacokinetics
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tat Gene Products, Human Immunodeficiency Virus/*administration & dosage/biosynthesis/pharmacokinetics
7.Diagnosis and treatment of epilepsy and narcolepsy comorbid.
Zhi-xian YANG ; Fang HAN ; Jiong QIN ; Xiao-yan LIU
Chinese Journal of Pediatrics 2013;51(9):676-678
OBJECTIVETo analyze the clinical diagnosis and treatment process of narcolepsy and epilepsy co-existence, and thereby to improve awareness of such cases.
METHODThe clinical manifestations of 2 cases were observed, and video-electroencephalogram (VEEG), multiple sleep latency tests (MSLT) were performed. Hypocretin 1 level in cerebrospinal fluid was examined in one case.
RESULTThe onset of disease of case one was started with epilepsy with myoclonic seizure. After half a year, catalepsy induced by emotion especially laughing and excessive daytime sleepiness appeared. MSLT was positive and hypocretin 1 level decreased. Narcolepsy-cataplexy was definitely diagnosed in this case. Valproate was given and seizure was controlled completely, but the excessive daytime sleepiness was aggravated. Combination of valproate, methylphenidate and clomipramine treatment improved the symptoms of narcolepsy and the patient was still free of epileptic seizures. The onset symptoms of case 2 were catalepsy and excessive daytime sleepiness. MSLT was positive. The treatment was ineffective because of bad compliance. After 2 years, episodes of impairment of consciousness with automatism occurred. VEEG showed slow waves and spikes in right temporal area. Complex partial seizure was determined. Oxcarbazepine was used and then the patients became seizures free, but the symptoms of narcolepsy were still obvious.
CONCLUSIONComorbidity of narcolepsy and epilepsy is a rare phenomenon. Clinical symptoms, predisposing factor, VEEG and MSLT can help diagnosis and differential diagnosis. The antiepileptic drugs might aggravate drowsiness. Based on therapy of epilepsy by using antiepileptic drugs, low dosage of central nervous system stimulants might improve the drowsiness and catalepsy symptoms of narcolepsy.
Adolescent ; Anticonvulsants ; administration & dosage ; therapeutic use ; Brain Waves ; physiology ; Central Nervous System Stimulants ; administration & dosage ; therapeutic use ; Child ; Comorbidity ; Diagnosis, Differential ; Electroencephalography ; Epilepsies, Myoclonic ; diagnosis ; drug therapy ; physiopathology ; Epilepsy ; diagnosis ; drug therapy ; physiopathology ; Humans ; Intracellular Signaling Peptides and Proteins ; cerebrospinal fluid ; Male ; Narcolepsy ; diagnosis ; drug therapy ; physiopathology ; Neuropeptides ; cerebrospinal fluid ; Orexins ; Polysomnography ; Sleep Stages ; physiology ; Treatment Outcome
8.Regulation function of Qingnao drop pilula to MARCKS mRNA express changes in acute cerebral ischemia hippocampus.
Yun-Ling ZHANG ; Qi-Hui ZHANG ; Wen BAI ; Zhen-Yun HAN ; Hong ZHENG ; Jin ZHANG ; Qi-Fu HUANG
China Journal of Chinese Materia Medica 2008;33(24):2938-2942
OBJECTIVETo observe the contribution of Qingnao drop pilula to the alteration of myristoylated alanine-rich C kinase substrate (MARCKS) mRNA expression in acute multi-infarction hippocampus.
METHODRat models of acute multi-infarction were established by injecting the embolus of blood powder through the right external carotid arteryinto the internal carotid artery, rats were randomly divided into five groups (n = 12 in each): normal, sham operation, model, Chinese medicine treatment, and Western medicine treatment. Qingnao drop pilula (133.28 mg x kg(-1)), nimodipine (7.25 mg x kg(-1)) were administered respectively to Chinese medicine treatment group and Western medicine treatment group by gavage, equal volume of normal saline were given to three groups. Rats were treated with drugs starting at 3rd day before the operation, one time per day. Observing morphologic changes in hippocampus by optical microscope and electron microscope. Detecting expression level of MARCKS mRNA in hippocampus by semi-quantification PCR method.
RESULTHippocampus cells arrange tidy, administrative levels were compactness in normal group, which cells differentially impaired in model group, Chinese medicine treatment group and Western medicine treatment group. Hippocampus cells damage of Chinese medicine treatment group have more reckless than the model group in histopathology. The MARCKS mRNA were expressioned in model group vs medication treatment groups, in Chinese medicine treatment group vs the model group.
CONCLUSIONQingnao drop pilula can alleciate histomorphology lesion of hippocampus when occurring acute multi-infarction, to turn slower MARCKS mRNA expression, may play a neuroprotective effect role through accommodating PKC-MARCKS signal transduction system.
Acute Disease ; Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Gene Expression Regulation ; drug effects ; Hippocampus ; drug effects ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Membrane Proteins ; genetics ; metabolism ; Myristoylated Alanine-Rich C Kinase Substrate ; Random Allocation ; Rats ; Rats, Wistar
9.The mechanism and treatment phases chosen of glycine for inhibition lipopolysaccharide induced Kupffer cells activation.
Zuo-jin LIU ; Hai-bo YOU ; Xu-hong LI ; Xian-feng CHEN ; Hai-zhong LIU ; Yong PENG ; Chang-an LIU ; Jian-ping GONG
Chinese Journal of Surgery 2006;44(3):189-192
OBJECTIVETo explore the possible mechanism and optimal treatment phase of glycine for inhibition lipopolysaccharide (LPS) induced Kupffer cells (KCs) activation.
METHODSThe KCs were isolated from 40 BALB/c mice and divided into four groups: the endotoxin group, the prevention group, the early treatment group and the later treatment group (n = 10). The endotoxin group was treated with 10 mg/L LPS, and in the other three groups, glycine (1 mmol/L) was given 24 h before, or at 0 h or 4 h respectively after LPS stimulation. At 0 h, 1 h, 2 h, 6 h and 12 h after LPS stimulation, the mRNA levels and protein expression of interleukin-1 receptor associated kinase-4 (IRAK-4) were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot respectively, and nuclear factor-kappaB (NF-kappaB) activities as well as tumor necrosis factor alpha (TNF-alpha) levels were also detected by enzyme-linked immunosorbent assay (ELISA).
RESULTSThe climax values of IRAK-4, NF-kappaB and TNF-alpha were significantly higher in the endotoxin group and the later treatment group than that in the other two groups (t = 3.17, 4.33, 2.47, 126.73, P < 0.01).
CONCLUSIONThe results indicated that prophylactic or simultaneous treatment with glycine could effectively inhibit LPS-induced KCs activation by inhibiting IRAK-4 expression.
Animals ; Cells, Cultured ; Drug Interactions ; Glycine ; administration & dosage ; pharmacology ; Interleukin-1 Receptor-Associated Kinases ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Kupffer Cells ; drug effects ; metabolism ; Lipopolysaccharides ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; NF-kappa B ; metabolism ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Time Factors ; Tumor Necrosis Factor-alpha ; metabolism
10.Differentiating effect of PPARgamma ligand rosiglitazone and all trans-retinoic acid on myeloma cells and its possible mechanism.
Hai-wen HUANG ; Guang-hua CHEN ; Hui-rong CHANG ; Howard C H CHOW ; Anska Y H LEUNG ; Raymond LIANG ; De-pei WU
Chinese Journal of Oncology 2009;31(12):885-889
OBJECTIVETo investigate the effects of PPARgamma ligand (rosiglitazone, RGZ) as well as combined with all trans-retinoic acid (ATRA) on human myeloma cells and try to explore the possible mechanism.
METHODSHuman myeloma cell lines U266 and RPMI-8226 cells were treated with RGZ in the presence or absence of ATRA. Cell proliferation was evaluated by [(3)H] thymidine incorporation, cell cycle distribution and CD49e expression were analyzed by flow cytometry, morphology changes were evaluated by Wright-Giemsa staining, and p27(Kip1) and p21(Waf1) expression was detected by Western blotting.
RESULTSThe exposure to RGZ induced proliferation inhibition in both cell lines in a dose-dependent manner. After cultured with 5 micromol/L RGZ, the proportion of U266 and RPMI-8226 cells in phase G(0)/G(1) was (45.2 +/- 6.7)% and (40.3 +/- 7.3)%, respectively (P < 0.05). The proportion of the cells in phase G(2)/M and S was (52.2 +/- 7.4)% and (57.4 +/- 9.5)%, respectively (P < 0.05). These changes were more evident when the RGZ concentration was increased to 10 micromol/L. A combination of RGZ with ATRA enhanced the growth inhibition and cell cycle arrest effects of RGZ. The RGZ-treated myeloma cells displayed morphological characteristics of cell differentiation, and more evident signs of differentiation were observed when RGZ was combined with ATRA. These changes were confirmed by the detection of CD49e expression. The expression of p27(Kip1) and p21(Waf1) in myeloma cells was up-regulated by RGZ and this change was more apparent when RGZ was used in combination with ATRA.
CONCLUSIONRGZ can induce cell cycle arrest and cell differentiation in myeloma cells which maybe caused by up-regulation of p27(Kip1) and p21(Waf1) expression. ATRA can enhance these effects of RGZ on multiple myeloma cells and combined use of these two drugs may show a synergistic effect on myeloma cells.
Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Integrin alpha5 ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Multiple Myeloma ; metabolism ; pathology ; PPAR gamma ; agonists ; Thiazolidinediones ; administration & dosage ; pharmacology ; Tretinoin ; pharmacology ; Up-Regulation