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Objective:To explore the potential value of interim 18F-fluorodeoxyglucose (FDG) PET/CT combined with B-cell lymphoma-2 (Bcl-2)/MYC protein dual expression (DE) status in the prognostic stratification for patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). Methods:Forty-six patients (21 males, 25 females; age 20-83 years) with newly diagnosed PGI-DLBCL from June 2012 to May 2019 in Nanjing Drum Tower Hospital were enrolled in this retrospective study. Immunohistochemistry for Bcl-2 and MYC protein expression was performed. All patients underwent baseline and interim (after 2-4 cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP) regimen) 18F-FDG PET/CT scans for assessment. Interim 18F-FDG PET/CT results were determined based on Deauville 5-point scale (DS) and changing rate of maximum standardized uptake value (ΔSUV max%) in 18F-FDG PET/CT images. Kaplan-Meier survival analysis, Cox proportional hazards regression model (single factor, multiple factors analysis) were used to analyze the prognosis (3-year progression free survival (PFS) and overall survival (OS) rates). Results:Patients were followed up for 6-84 months, and 14 showed disease progression and 9 died. The PFS rate and OS rate were 69.6% and 80.4%, respectively. DE, DS as well as ΔSUV max% were significant predictors of PFS (hazard ratio ( HR) values: 3.280, 5.120, 9.167, all P<0.05); lactate dehydrogenase (LDH), MYC protein expression, DS and ΔSUV max% were significant predictors of OS ( HR values: 4.091, 9.618, 7.697, 11.151, all P<0.05). Multivariate analysis revealed that DS and ΔSUV max% were independent predictors of PFS and OS ( HR values: 4.370-9.244, all P<0.05). In the DS negative (-) group, patients with DE positive (+ ) had lower PFS and OS rates than those with DE- (PFS rate: 50.0% vs 88.9%; OS rate: 66.7% vs 96.3%; χ2 values: 6.050, 4.966, both P<0.05). In ΔSUV max%<90% group, patients with DE+ had lower PFS rate than those with DE- (12.5% vs 68.8%; χ2=6.649, P=0.01). Conclusions:Interim PET/CT analysis using DS and ΔSUV max% is able to predict survival in PGI-DLBCL patients. The combination of DS, ΔSUV max% and DE can risk-stratify PGI-DLBCL patient more effectively.
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Objective: By observing the effects of electroacupuncture (EA) on the apoptosis of conjunctival cells of rabbits with dry eye syndrome (DES) and the expressions of apoptosis-related proteins Caspase-3, Fas and Bcl-2, to discuss the mechanism of EA in the treatment of DES from the perspective of cell apoptosis. Methods: Male New Zealand rabbits were randomly divided into a normal group (NG), a model group (MG), an EA group (EAG) and a sham EA group (SEAG). DES rabbit model was developed by eye drop of 0.1％ benzalkonium chloride. The rabbit tear secretion and tear film break-up time (BUT) were measured; terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptosis of conjunctival cells; the expressions of Caspase-3, Fas and Bcl-2 proteins in conjunctival cells were detected by immunohistochemistry. Results: Compared with the NG, the rabbit tear secretion decreased and the BUT was shortened in the MG (both P<0.01); compared with the MG and the SEAG, the rabbit tear secretion increased and the BUT was prolonged in the EAG (all P<0.05). Compared with the NG, the apoptosis of rabbit conjunctival cells increased (P<0.01), the expressions of Caspase-3 and Fas proteins increased (both P<0.05), and the expression of Bcl-2 protein decreased (P<0.01) in the MG; compared with the MG and the SEAG, the apoptosis of rabbit conjunctival cells decreased (both P<0.01), the expressions of Caspase-3 and Fas proteins decreased (all P<0.05), and the expression of Bcl-2 protein increased (both P<0.01) in the EAG. Conclusion: EA can inhibit the apoptosis of rabbit conjunctival cells, down-regulate the expressions of apoptosis-related proteins Caspase-3 and Fas, and up-regulate the expression of Bcl-2 protein, which may be one of the mechanisms of EA in treatment of DES.
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Objective @#To investigate the effect and mechanism of allicin combined with 5-FU on proliferation inhibition and apoptosis of the mucoepidermoid carcinoma MEC-1 cell line in mucoepidermoid carcinoma in order to provide the corresponding basis for subsequent clinical drug application.@*Methods @# MEC-1 cells in the logarithmic growth phase were randomly divided into control groups and experimental groups. The control groups were PBS groups containing 0.1% DMSO, while the experimental groups were the allicin group, 5-FU group and combined drug group (the allicin combined with the 5-FU group). The proliferation inhibition rates of allicin, 5-FU and allicin combined with 5-FU in MEC-1 cells were detected by the CCK8 method at different concentrations (0, 25, 50, and 75 mg/L) for 24 h, and the IC50 value of allicin and 5-FU after 24 hours was calculated. The apoptotic rate of MEC-1 cells treated with allicin, 5-FU and allicin combined with 5-FU at different concentrations (0, 25, 50, and 75 mg/L) for 24 hours was measured by flow cytometry. The expression of Bax and Bcl-2 protein was determined by Western blot analysis of the IC50 concentration of allicin and 5-FU alone and in combination with MEC-1 cells for 24 hours. @*Results@#The growth inhibition rate and apoptosis rate of MEC-1 cells in the combined drug group were higher than those in the allicin group and the 5-FU alone group (P < 0.01). Allicin and 5-FU alone and in combination downregulated Bcl-2 protein and upregulated Bax protein expression, and the combined drug group had the largest ratio of Bax/Bcl-2 (P < 0.05). @*Conclusion @#Allicin and 5-FU both alone and in combination can inhibit the proliferation of and induce apoptosis in MEC-1 cells, and allicin can enhance the apoptosis of 5-FU in MEC-1 cells, which may be related to the apoptosis of the mitochondrial pathway.
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Objetivo: realizar un estudio descriptivo sobre Cáncer Colorrectal en Cova da Beira Portugal y el valor pronóstico de BCL2 en asociación con la localización del tumor,Estadificación TNM, y tipo histológico. Materiales y Métodos: se realizó un estudio en 29 pacientes que tuvieron cirugía curativa para la escisión de Cáncer Colon Rectal (CCR) en Centro Hospitalario Cova da Beira con el objetivo de verificar si la presencia de la oncoproteína BCL2 en células neoplásicas es un factor predictivo del pronóstico,verificando también si es predictivo de la estadificación TNM, localización y diferenciación celular en el Cáncer Colon Rectal. Resultados: los hallazgos de este estudio coinciden con lo reportado en la literatura, se encontró que la incidencia del CCR es mayor en hombres que en mujeres, el riesgo de la enfermedad aumenta con la edad y la localización más frecuente de lesión neoplásica es en la porción izquierda del colon,con un total de 26 casos (89,65%). Además, se encontró asociación estadística de la expresión de BCL2 con el pronóstico y con la diferenciación histológica. Conclusión:a pesar de las limitaciones de este estudio, los datos hallados guardan relación con lo reportado en la literatura y establecen una asociación estadística de la expresión de BCL2 con el pronóstico y con la diferenciación histológica..(AU)
Objective: to carry out a descriptive study on Colorectal Cancer in Cova da Beira Portugal and the prognostic value of BCL2 in association with tumor location, TNM Staging, and histological type.Materials and Methods: a study was conducted in 29 patients who had curative surgery for Rectal Colon Cancer (CRC) excision in the Cova da Beira Hospital Center with the objective of verifying whether the presence of the BCL2 oncoprotein in neoplastic cells is a predictive factor of the prognosis, also verifying if it is predictive of TNM staging, localization and cell differentiation in Rectal Colon Cancer. Results: the findings of this study coincide with that reported in the literature,it was found that the incidence of CRC is higher in men than in women, the risk of the disease increases with age and the most frequent location of neoplastic lesion is in the left portion of the colon, with a total of 26 cases (89.65%). In addition, statistical association of BCL2 expression with prognosis and with histological differentiation was found. Conclusion: despite the limitations of this study, the data found are related to that reported in the literature and establish a statistical association of BCL2 expression with prognosis and histological differentiation..(AU)
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Humans , Colorectal NeoplasmsABSTRACT
Aims: It’s known that apoptosis, necessary for renewal and vital activity of cells, is suppressed in the tumour cell. The strategies of anti-cancer therapy may be a search of the new drugs and development of targeted substances, including the Bcl-2 family proteins, to initiate apoptosis. One of such drugs may be spatially substituted phenol anphen sodium (AS), a derivative of dibunol that can inhibit free radical oxidation and interact with peroxide radicals in the cell, and has also biological activity. The study aims to investigate possible anti-cancer, antioxidant AS action on experimental tumours of the ascitic sarcoma 37 and Lewis carcinoma of F1 (C57Bl × DBA) mice. The influence of AS drug on Bcl-2 family proteins level in blood plasma Lewis carcinoma cells suspension in spleen cells of white mice was determined. Place and Duration of Investigation: Emanual Institute of Biochemical Physics Russian Academy of Sciences, Moscow, Russia, between October 2013 and March 2018. Metodology: To examine AS anti-cancer properties, the kinetic curves of tumour development and the number of ascitic cells in ascitic fluid were studied; the changes in anti-apoptotic Bcl-2 proteins and Bcl-2 family proteins levels were monitored by immunoblotting. Results: A significant (100%) anti-tumour effect of the antioxidant sodium antepoxide AS (2- (carboxy) -2- (N-acetylamino) -3- (3 ', 5'-di-t-butyl-4'-hydroxyphenyl) - sodium propionate was seen when it was administered to mice after transplantation of ascites sarcoma cells 37. The reduction of the Bcl-2 protein took place in the blood plasma of F1 mice (C57B1 × DBA), when AS (10-4M) was administered to mice before transplantation by Lewis cells of carcinoma, as shown by immunoblotting. At the same time, this did not change the survival rate of mice. The administration of AS into the Lewis carcinoma cell suspension causes a dramatic decrease in the amount of monomer and homodimer of Bcl-2 protein for 1-3 hours in these cells. AS drug administered during 4 days (10-4 M) to white mice caused a change in the ratio of Bcl-2 family proteins in the spleen cells, indicating the onset of the mitochondrial pathway of apoptosis. Conclusion: The anti-cancer effect of AS can be associated with an effect on the molecular targets of the apoptosis pathway, including the proteins of the Bcl-2 family.
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Objective@#To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL).@*Methods@#Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis.@*Results@#The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis.@*Conclusions@#Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.
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Objective To investigate the effect of ulinastatin on myocardial injury in rats with sepsis.Methods Thirty male SD rats were randomly (random number) divided into 3 groups:sham operation group (Sham group,n=10),sepsis group (sepsis group,n=10) and ulinastatin group (UTI group,n=10).The sepsis model of the rats was subjected to cecal ligation and puncture (CLP).Rats of UTI group were given 200 000 U/kg ulinastatin at 6 hour after modeling,and dosing was repeated every 12 h.Blood samples were collected from inferior vena cava at 6,12,24,36 h after modeling for determination of cardiac troponin-Ⅰ (cTnI) and the inflammatory factor by ELISA,then the rats were sacrificed and hearts were removed for myocardial tissue stained with hematoxylin eosin (HE) staining,the expression of Bax/Bcl-2 protein level and myocardial cell apoptosis were detected by TUNEL.The level of caspase-3 protein in myocardial tissue was detected by Western-blot.Results The level of cTnI (ng/mL) in serum in UTI group at 6,12,24 and 36 h after modeling were significantly lower compared with sepsis group(P＜0.05).The protein expression levels of TNF-α and IL-6 (ng/mL) in group UTI were higher than those in Sham group,but was significantly lower than those in Sepsis group (P＜0.05).HE staining showed that inflammatory cell infiltration present in myocardial cells,edema and vacuole formation were observed in sepsis group,while those were significantly attenuated in UTI group compared with sepsis group.UTI increased the level of myocardial Bcl-2 protein in the rats (P＜0.05),and reduced the level of myocardial Bax protein (P＜0.05).TUNEL and HE staining showed apoptosis cells in UTI group was significantly reduced compared with sepsis group [(32.2±4.8)％ vs.(58.4±5.6)％,P＜0.05];Western-blot method showed the level of Caspase-3 protein in UTI group was higher than that in group sham (0.32±0.048) vs.(0.12±0.03),P＜0.05],but significantly lower than that of Sepsis group [(0.32±0.048) vs.(0.55±0.052),P＜0.05].Conclusions Ulinastatin can reduce proinflammatory mediators release in the blood of sepsis rats,and inhibit the apoptosis of myocardial cells protecting myocardial cells through the regulation of the Caspase-3 pathway during sepsis.
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Mitochondrion is an important organelle in cells and plays a crucial role in tumor development. Therefore, improvement of the targeting ability of anticancer drugs to mitochondria will increase the treatment efficacy for tumor and reduce the side effect on normal tissues. Here, research progresses in mitochondrial targeting have been reviewed in three aspects for tumors treatment: the potential, permeability and translocase of mitochondrial membrane. The review provides a reference for the development of mitochondria targeted therapeutic systems.
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Targeting cell apoptosis is currently the most promising therapy for cancer treatment. The BH3-only protein, which is a member of Bcl-2 family, can bind to the pro-survival members of the family and neutralize their functional activities to induce apoptosis (ie, to isolate pro-apoptotic members of the Bcl-2 family). BH3 mimetics, a kind of small molecule compounds, has the ability to mimic the BH3-only protein to induce apoptosis. The prototype of BH3 mimetics is ABT-737, who can selectively targets on BCL-XL, BCL-2 and BCL-W (but not MCL-1 and A1). ABT-263, a derivative of ABT-737, has a better performance of inducing apoptosis and inhibiting the growth of tumor in clinical trials. At this stage, some presumably BH3 mimetics has entered the clinical stage, while a large part of them is still being characterized and tested. Basing on the mechanism of BH3-only protein, this review summarize a variety of BH3 mimetics which have been widely recognized, and show the latest developments of newly diagnosed BH3 mimetics in the field.
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Objective Toexplore expression and clinical significance of WWOX protein and the Bcl-2 protein in the organiza-tion of bronchial lung cancer (primary lung cancer).Methods Chose 76 lung cancer patients with clear pathological diagno-sis who were hospitalized in the Shaanxi Provincial People’s Hospital from 2010 and 2015(including 29 cases of adenocarci-noma,27 cases of squamous cell carcinoma,and 20 cases of small cell carcinoma)and 7 cases of normal lung tissue,8 cases of lung tuberculosis.The expressions of WWOX protein,Bcl-2 protein and more that 5 cm normal lung tissue adjacent to carci-noma were measured by immunohistochemistry SP method.The expression difference between patients and normal control group and the influence of sex,age,pathological type,differentiation degree,clinical stage,lymph node metastasis,smoking index on the expression of WWOX protein and Bcl-2 protein in lung cancer were analyzed.Results ①The positive expres-sion rate of WWOX protein in lung cancer group (35.52%)was significantly lower than that in normal lung tissue (73.33%,P<0.05).The positive expression rate of Bcl-2 protein in lung cancer group (78.06%)was significantly higher than that in control group (23.75%,P<0.05 ).②The positive expression rate of WWOX protein in male patients (21.43%)was significantly lower than that in female patients (52.94%),and the difference was statistically significant (χ2=8.146,P=0.04).The positive expression rate of Bcl-2 protein in male patients (71.43%)was significantly higher than that in female patients (35.29%),the difference was statistically significant (χ2=9.923,P=0.002).③In lung cancer with lymph node metastasis,the positive rate of WWOX protein (17.07%)was significantly lower than that in non-lymph node metastasis (48.57%),and the difference was statistically significant (χ2=8.67,P=0.003).In lung cancer with lymph node metastasis,the positive rate of Bcl-2 protein expression (68.29%)was significantly higher than that in non-lymph node me-tastasis (34.28%),and the difference was statistically significant (χ2=8.758,P=0.003).④The positive rate of expression of WWOX protein in patients whose smoking index≥400 and in patients that<400 was 15.63% and 47.73%,respectively, the differences were significant (χ2=8.48,P=0.003).The positive rate of expression of Bcl-2 protein in patients whose smoking index≥400 and in patients that<400 was 56.25% and 22.73%,respectively,the differences were significant (χ2=8.947,P=0.003).⑤WWOX and Bcl-2 protein expressions had no obvious relationship with ages,pathological type,degree of differentiation and clinical stage.⑥WWOX protein expression had negative correlation with Bcl-2 protein expression in lung cancr tissues.Conclusion WWOX protein expression in lung cancer was lower than that in adjacent normal lung tis-sue,Bcl-2 protein expression in lung cancer tissues was higher than that in adjacent normal lung tissue.WWOX protein ex-pression had negative correlation with Bcl-2 protein expression in lung cancer tissues.
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OBJECTIVE: To observe the effect of Biochanin A (Bio A) on rat hippocampal neurons injuries impaired by H2O2 and Bcl-2, Bax and caspase-3 protein expression. METHODS: Hippocampal neurons of newly born rat were cultured in vivo and were injured by H2O2. Different concentration of Bio A on cell viability was measured by CCK-8; cell apoptosis rate was tested by flow cytometry analysis; Bcl-2, Bax and caspase-3 protein expression were tested by Western blot method. RESULTS: Compared with the model group, Bio A significantly improved hippocampal neurons cell viability and inhibited cell apoptosis and necrosis. In addition, Bio A clearly enhanced the protein expression of Bcl-2 and decrease the protein expression of Bax and caspase-3. CONCLUSION: The protective effect of Bio A on rat hippocampal neurons injuries impaired by H2O2 may be related to the inhibition of hippocampal neurons apoptosis. The mechanism of Bio A against cell apoptosis may involve the increased Bcl-2 protein expression and reduced Bax, caspase-3 protein expression.
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Objective:To observe the effect of Gemcitabine ( GEM) on the viability and apoptosis of non-small cell lung cancer HCC827 in vitro. Methods:The cell viability,apoptosis and cell cycle of HCC827 cells induced by Gemcitabine were detected with cell counting kit-8 assay (CCK-8),Annexin V-FITC/PI staining and flow cytometry. The expression of Bcl-2 protein of cells treated with GEM was examined by Western blot assay. Results: There was significant inhibition effect on HCC827 cells treated with 0. 1-1 000 ng/ml of GEM,which can promote the occurrence of HCC827 cell apoptosis and arrest cell in the S phrase. The apoptosis induced by GEM was accompanied with the down regulation of Bcl-2 protein. Conclusion: GEM can inhibit the cell viability and induce the HCC827 cell apoptosis and S phrase arrest. Its cell dead type was apoptosis,which was related with the expression of Bcl-2 protein.
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Objective To explore the effects of dipeptidyl peptidase ( DPP-4 ) inhibitor on proteins expression of Bcl-2 and Bax of islet β-cells through increasing the expression of islet γ amino acid butyric acid ( GABA) . Methods A total of 50 rats of clean grade were studied. Among them, ten rats were randomly selected as normal controls, the remaining forty rats were fed with high-fat diet and then intraperitoneal injection with streptozotocin, the diabetic rats models were then established. Rats were randomly divided into three groups:i. e. diabetic control group, DPP-4 inhibitor group, and antagonist group ( DPP-4 inhibitor and GABA receptor antagonist). Six weeks later, blood glucose, serum insulin, glucagon, and the proteins expression of GABA, Bcl-2, and Bax of islet β-cells were measured. Results ( 1 ) Compared with diabetic control group, serum insulin was increased(P<0.05),bloodglucoseandserumglucagonweredecreasedinDPP-4inhibitorgroup(P<0.05). (2) Compared with DPP-4 inhibitor group, serum insulin was decreased(P<0. 05), blood glucose and serum glucagon were increased(P<0. 05) in antagonist group. (3) Compared with diabetic control group, the expression of GABA was increased(P<0. 05), the expression of Bcl-2 protein was increased (P<0. 05) in pancreatic β-cells in DPP-4 inhibitor group. ( 4 ) Compared with diabetic control group, the expression of GABA in pancreatic β-cells was increased in antagonist group(P<0. 05) . Compared with DPP-4 inhibitor group, the expression of Bax protein in pancreaticβ-cells was increased in antagonist group(P<0. 05) , while the expression of Bcl-2 protein was decreased (P<0. 05). Conclusions DPP-4 inhibitor could increase the secretion of insulin, decrease the secretion of glucagon, up-regulate expression of anti-apoptosis protein Bcl-2, and down-regulate expression of apoptosis protein Bax in pancreatic β-cells through increasing the expression of GABA, inhibiting pancreatic β-cells apoptosis and protecting the damagedβ-cells in type 2 diabetic rats.
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OBJECTIVE: To investigate the mechanism of inhibition and radiosensitization effects of combining treatment with tanshinone I and(irradiation) IR on mice bearing Lewis lung carcinoma(LLC). METHODS: The models of LLC in C57BL/6 mice were established via subcutaneous injection of mouse LLC cells, and divided into model control group, radiation alone group, Tan I (40 mg · kg-1) group, 5-Fu + IR group, Tan I (10, 20, 40 mg · kg-1) + IR groups. After irradiated, the relative volume of tumor was observed, the delay time of tumor growth and enhancement factor (EF) was calculated. After stripped, the inhibition rate was calculated. Cell apoptosis index( AI) was in vestigated by TUNEL staining. The protein expressions of Bcl-2 and Bax were detected by Western blot. RESULTS The different concentrations of Tan I (low, medium and high) + IR groups inhibited the tumor growth significantly, and the inhibition rate was 27.14%, 38.46%, 59.78%, respectively, which were significant difference as compared with IR group (P < 0.01). And also had the significant radiosensitizing effect, the enhancement factor was 1.09, 1.76, 2.03, respectively. The AI was 51.3% in Tan I (H) + IR group, which was significant difference as compared with IR group(P < 0.05). The expression of Bcl-2 protein was decreased, and Bax proteins was increased by combining treatment with Tan I and IR. CONCLUSION Combining treatment with Tan I and IR inhibited the tumor growth and had radiosensitizing effects in mice bearing LLC. One of the mechanism may be that it might induce apoptosis by regulated the expression of Bcl-2/Bax protein, so cells were more sensitive to radiation.
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Objective To explore inhibitory effects of ginsenoside on the proliferation of human thyroid canc-er SW579 cells in vitro and expression of C -myc and Bcl -2 protein.Methods Human thyroid cancer SW579 cells were cultured according to conventional method.The study was divided into the control group and ginsenoside group (20,40,8ug/mL).Inhibitory role of ginsenoside on proliferation of SW579 cells was detected by MTT assay.Western-blot method was used to determine expression levels of C -myc and Bcl -2 protein in different group.Results The inhibition rates of 20,40,80μg/mL ginsenoside to SW579 thyroid carcinoma cell were 22.35%,51.76% and 68.24% respectively.Which meaned ginsenoside had obvious inhibitory effect compared with the control group(P <0.01),and inhibition increased with the increase of solubility(P <0.01).C -myc and Bcl -2 protein were reduced progressively in place with the increase of ginsenoside concentration by Western -Blot analysis (P <0.01 ).Conclusion Gisenoside may play the inhibitory role on proliferation of human thyroid cancer SW579 cells in vitro, and its mechanism may be related with down -regulation of C -myc and Bcl -2 protein.
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OBJECTIVE: To investigate the relationship between myocardial ischemia-reperfusion injury and Bcl-2 family proteins regulating autophagy were searched, and elaborated the mechanism of Bcl-2 family proteins affecting myocardial ischemia-reperfusion injury by regulating autophagy. METHODS: The literatures which related to myocardial ischemia-reperfusion injury and Bcl-2 family proteins regulating autophagy were searched. The review is finished by analyzing and organizing the literatures. RESULTS AND CONCLUSION: In early ischemia, appropriate autophagy of myocardial cells can reduce the degree of ischemia-induced myocardial injury, however, in the reperfusion period, excessive activation of autophagy can aggravate myocardial cell injury. Bcl-2 family proteins are important regulation factors of autophagy, it can play an important role by interacting with other relevant factors contained in autophagy pathway during the two different periods of myocardial ischemia and reperfusion injury.
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AIM:To investigate matrine-induced apoptosis of human medulloblastoma D 341 cells and the ex-pression of Bax , Bcl-2, serine/threonine kinase Akt and phosphorylated Akt ( p-Akt) in vitro.METHODS: D341 cells were divided into experimental groups ( added with matrine at different concentrations ) and control group ( under the same conditions without matrine).The proliferation of D341 cells was analyzed by CCK-8 assay.Apoptosis was detected by An-nexin V-FITC/PI double staining and the expression of Bax , Bcl-2, Akt and p-Akt was detected by Western blotting .RE-SULTS:Matrine significantly inhibited the proliferation of D 341 cells and increased the apoptosis in a dose-and time-de-pendent manner .The cell apoptosis was characterized by chromatin condensation with margination of chromatin to the nu -clear membrane , increased when and larger cytoplasmic vacuoles , and formation of apoptotic body after treatment with ma-trine.The expression of Bax increased , while the expression of Bcl-2 and p-Akt decreased when the drug concentration gradually increased .CONCLUSION:Matrine induces the apoptosis of human medulloblastoma D 341 cells in vitro by acti-vation of Bax, down-regulation of Bcl-2 and reduction of p-Akt expression level in the PI3K/Akt signaling pathway.
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AIM:To explore the effect of Vaccinium vitis procyanidin on the growth of glioma cells .METH-ODS:Glioma C6 cells were cultured and divided into control and 10, 20 and 40μg/L Vaccinium vitis procyanidin groups . The influence of Vaccinium vitis procyanidin on the growth of C 6 cells was measured by MTT assay and the observation un-der inverted microscope .The apoptotic rate was detected by Annexin V/PI staining .The protein expression of Bcl-2 and Bax was determined by immunocytochemistry .The protein levels of Bcl-2, Bax and caspase-3 were also examined by West-ern blotting .RESULTS:The growth of C6 glioma cells was inhibited by Vaccinium vitis procyanidin at concentrations of 10, 20 and 40 μg/L.The growth was significantly inhibited in 40 μg/L Vaccinium vitis procyanidin group at 24 h and 48 h, and in 20 and 40 μg/L Vaccinium vitis procyanidin groups at 72 h (P<0.01).The density of the cells was decreased when the concentration of Vaccinium vitis procyanidin increased .The apoptotic rate was increased when the concentration of Vaccinium vitis procyanidin increased either .The expression of Bcl-2 was decreased and Bax was increased after 10, 20 and 40 μg/L Vaccinium vitis procyanidin treatments .The ratio of Bax/Bcl-2 was increased when the dose of Vaccinium vitis pro-cyanidin increased (P<0.05 or P<0.01).The expression of Bcl-2 was decreased (P<0.01), and Bax and caspase-3 were increased after 10, 20 and 40 μg/L Vaccinium vitis procyanidin treatments .The ratio of Bax/Bcl-2 was increased when the dose of Vaccinium vitis procyanidin increased (P<0.01).CONCLUSION:Vaccinium vitis procyanidin inhibits the growth of glioma cells by down-regulating Bcl-2 protein and up-regulating Bax protein to activate caspase-3, thus indu-cing apoptosis .
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Aim Toinvestigatetheeffectsoftriptonot-erpene methyl ether ( TME ) , a diterpene derived from the medicinal plant Triptergium wilfordii, on human gastric cancer AGS cell proliferation inhibition and ap-optosisinducedinvitro.Methods MTTassaywas used for screening tumor spectrum and detecting the vi-ability of AGS cells and normal human gastric epitheli-al cells GES-1 . Cell morphology was observed by light microscopy and AO / EB staining. Flow cytometry was used to detect cell apoptotic rate and cell cycle. JC-1 staining and fluorescence probe DCFH-DA were em-ployed to detect the changes of mitochondrial mem-brane potential and reactive oxygen species ( ROS ) . The effect of inhibiting AGS clonogenic survival was as-sayed by the method of plate clone formation. Western blot was used to analyse the expression of caspase-3 , caspase-8,Bcl-2andBax.Results MTTresults showed that TME exhibited significantly higher cytotox-icity to gastric cancer AGS cell line than to noncancer-ous cell line GES-1. IC50 for AGS of 48 h treatment was 23 . 85 μmol · L-1 . TME significantly inhibited colony formation and caused morphological changes in AGS cells. Annexin V-FITC / PI double staining showed the apoptotic rate increased. DCFH-DA stai-ning showed TME resulted in an increase in intracellu-lar ROS levels. Mitochondrial membrane potential de-creased after TME treatment. Western blot results showed that TME increased the proportion of Bax /Bcl-2 , with the activation of caspase-8 and caspase-3 . The broad-spectrum caspase inhibitor z-VAD-fmk pre-treatment reduced the expression of caspase-8 and caspase-3. TME enabled AGS cell cycle arrest in G0/G1phase.Conclusion TMEpossessespotenttumor selected toxicity and can induce apoptosis of AGS cells through cell cycle arrest, which is associated with Bcl-2 protein family.
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Objective To explore the condition of MYC/BCL2 protein coexpression in 245 patients with diffuse large B-cell lymphoma (DLBCL)and to find the correlations among MYC/BCL2 protein coexpres-sion,the germinal center B-cell-like (GCB)subtype and non-GCB subtype.Methods Paraffin-embedded lymphoma samples from 245 patients with DLBCL were studied using immunohistochemistry for MYC,BCL2, CD10,BCL6,MUM1 and KI67.And the protein expressions of them were analyzed.Results In the speci-mens of 245 patients with DLBCL,the patients with non-GCB were 163 (66.5%),and the patients with GCB were 82 (33.5%).The group of MYC/BCL2 protein coexpression comprised 35.9% (88/246)of the all patients.Non-GCB subtype group had a significantly higher frequency of MYC/BCL2 protein coexpression than the GCB subtype group (41.7%∶24.4%;χ2 =7.116,P=0.008).Conclusion The data shows that MYC/BCL2 protein coexpression occurs significantly more commonly in the non-GCB subtype.We can predict prog-nosis and choose therapeutic regimen base on the assessment for MYC and BCL2 protein expression.