ABSTRACT
Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.
Subject(s)
Animals , Humans , Mice , Apoptosis , Brucea/chemistry , Glycogen Synthase Kinase 3 , Jurkat Cells , Phosphatidylinositol 3-Kinases/genetics , Plant Oils/pharmacology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Proto-Oncogene Proteins c-akt/genetics , Seeds/chemistry , Signal TransductionABSTRACT
Objective@#To investigate the effect of brucea javanica oil emulsion (BJOE) on the proliferation, collagen synthesis and ERK1/2 MAPK singaling pathway of hypertrophic scar fibroblasts (HSFs).@*Methods@#The human hypertrophic scar tissues were collected, and HSFs were isolated, cultured and identified in vitro. Cells were treated with BJOE under the concentration of 0.5, 1, 5, 10, 20 and 50 mg/ml for 24 h respectively; the half inhibitory concentration(IC50)of 24 h was calculated. The experimental groups were treated for 24, 48, 72 h by BJOE at the IC50, the control group was conventionally cultured without BJOE. Cell proliferation was detected by CCK-8 assay and cell cycle was determined by flow cytometry (FCM). The morphological changes of cells treated with BJOE at a concentration of IC50 for 24 h were observed. The protein expression levels of collagen Ⅰ, vimentin, ERK1/2 and p-ERK1/2 were measured by Western blot.@*Results@#The IC50 of BJOE was 1.176 mg/ml, so the concentration of 1 mg/ml was selected for the subsequent experiment. After 24, 48, 72 h treated with BJOE at a concentration of 1 mg/ml, the inhibition rates of BJOE on HSFs were (53.13±2.40)%, (75.07±2.67)%and (88.65±0.32)%, respectively. The difference was significant (P<0.05). Under the effect of BJOE, the number of HSFs significantly decreased, the interval between cells widened, cell protrusions were significantly shortened or even disappeared, and the cells became round. The percentage of cells decreased in S phase. Expression of type Ⅰ collagen, vimentin and p-ERK1/2 in HSF was significantly inhibited (P<0.05), while there was no significant difference in the expression of ERK1/2(P>0.05).@*Conclusions@#BJOE inhibites the proliferation of HSF and the synthesis of type Ⅰ collagen, and its mechanism is related to the inhibition of ERK1/2 phosphorylation and vimentin expression.
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This study was aimed to systematically evaluate the clinical efficacy and safety of brucea javanica oil emulsion injection combined with gemcitabine plus cisplatin (GP) regimen in the treatment of non-small cell lung cancer.Literatures were retrieved from databases of CNKI,Wanfang database,VIP,CBM,Pubmed from the date of database establishment to March 2017.Journals on related fields were also manually searched.The randomized controlled trials (RCTs) of brucea javanica oil emulsion injection combined with GP regimen in the treatment of non-small cell lung cancer were collected.The results showed that there were 12 included RCTs with 1 118 patients.The meta-analysis results showed that compared with single using of GP regimen,there were statistical significance in the partial remission rate [OR =1.59,95％ CI (1.23,2.05),P =0.000 4],the total remission rate [OR =1.72,95％ CI (1.33,2.22),P ＜ 0.000 1],the KPS (Karnofsky) score improvement [OR =2.59,95％ CI (1.96,3.43),P ＜ 0.000 01],the deterioration of KPS score [OR =0.33,95％ CI (0.25,0.46),P ＜ 0.000 01],the incidence of bone marrow suppression [OR =0.48,95％ CI (0.35,0.65),P ＜ 0.000 01],and the incidence of gastrointestinal adverse reactions [OR =0.46,95％ CI (0.23,0.91),P =0.03] by brucea javanica oil emulsion injection combined with GP regimen in the treatment of non-small cell lung cancer.It was concluded that brucea javanica oil emulsion injection combined with GP regimen can increase clinical efficacy,decrease myelosuppression rate and gastrointestinal adverse reactions.
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Eligible studies were searched in Cochrane library, Pubmed, Medline, CBM, CNKI and VIP databases from establishment to June 2014. Two researchers independently identified 7 randomized controlled trials (RCTs) and extracted data of Brucea javanica oil emulsion injection combined with chemotherapy. Based on the published studies, the researchers analyzed them by RevMan 5.2 software and investigated the efficacy and safety of Brucea javanica oil emulsion injection combined with chemotherapy for patients with advanced gastric cancer by Meta analysis. Meta analysis showed that, compared with the simple chemotherapy, Brucea javanica oil emulsion injection combined with chemotherapy could increase objective response rate by 43%(RR=1.43, P<0.001). In addition, the incidence of neutropenia (RR=0.56, P<0.001), thrombocytopenia (RR=0.64, P=0.02), nausea, vomit (RR=0.66, P=0.002) decreased in these patients. However, the quality of life was not improved significantly in gastric carcinoma patients with combined therapy (RR=1.36, P=0.07). The paper suggested Brucea javanica oil emulsion injection combined with chemotherapy could increase efficacy and safety, which might be a promising therapy for patients with advanced gastric cancer.
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Objective To evaluate the efficacy and untoward effects of brucea javanica oil emulsion combined with radiotherapy in the treatment of patients with esophageal cancer. Methods 50 initial treatment patients with esophageal squamous cell carcinoma were randomly assigned to observation group (25 cases) and control group (25 cases). All patients were treated with three dimensional conformal intensity modulated radiation therapy (3D-IMRT) and the radiation dose was 64 Gy/32 times (95 % PTV). The patients in observation group received the treatment of brucea javanica oil emulsion during radiotherapy. The differences between the two groups were compared in respect of the efficacy, the adverse reactions and the quality of life (QOL). Results The effective rate in observation group was 92%(23/25) and it was 68%(17/25) in control group, there was significant difference between the two groups (χ2 = 4.500, P= 0.034). The incidence of radiation esophagitis at the level of RTOG2 and above in observation group was 20%(5/25) and it was 60%(15/25) in the control group, there was significant difference between the two groups (χ2= 8.333, P=0.004). The improvement rate of QOL in observation group was 68 % (17/25) and it was 40 % (10/25) in control group, there was significant difference between the two groups (χ2 = 3.945, P= 0.047). Conclusion Brucea javanica oil emulsion combined with radiotherapy for the treatment of patients with esophageal cancer can improve the therapeutic effect and QOL,it can also reduce radiation reactions.
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Objective To evaluate short -term clinical efficacy and adverse effects of brucea javanica oil emulsion(BJOE)combined with TP regimen in treating malignant pleural effusion(MPE)of non -small cell lung cancer(NSCLC)by double -way chemotherapy.Methods Totally 91 patients with MPE of NSCLC diagnosed by pathology were builted into the central venous catheter.The patients were assigned to group A,B and C according to therapies.Group A(21 cases)accepted infusion of BJOE 60mL into thoracic cavity twice a week.Group B(33 cases) accepted TP regime therapy,which included paclitaxel(TAX)intravenous chemotherapy at a dose of 150mg/m2 and cisplatin(DDP)injecting into thoracic cavity at a dose of 60mg +0.9% sodium chloride injection 30mL in first day, the therapy was repeated every 3 weeks.Group C(38 cases)combined the therapies of group A′s and B′s.Clinical efficacy and adverse effects were evaluated after 6 weeks.Results The objective response rate(81.6%)for group C was higher than group A or B(χ2 =8.605,P <0.05),the same result were in CR ratio(55.3%)(χ2 =10.384,P <0.05)and PD ratio(5.3%)(χ2 =8.649,P <0.05).There were no serious adverse effects in the three groups.The occurring rate of white blood cell reduction in group A was lower than those of group B and C,there was statistically significance(χ2 =8.999,P <0.05).Conclusion The efficacy of BJOE combined with TP regimen in treating MPE of NSCLC by double -way chemotherapy is better than that of single chemotherapy or alone intrathoracic treatment, and the adverse effects could be well tolerated.
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Objective To compare the efficacy between the brucea javanica oil emulsion combined with the whole radiotherapy group (treatment group) and only radiotherapy group (control group) in non-small cell lung cancer patients with brain metastases.Methods The clinical data of 53 non-small cell lung cancer patients with brain metastasis were retrospectively reviewed,including 27 cases in treatment group and 26 cases in control group.Results The remission rates were 77.8 ％ (21/27) and 69.2 ％ (18/26) respectively in treatment group and control group.The improvement rates of Kamofsky in the treatment group and control group were 66.7 ％ (18/27) and 30.8 ％ (8/26),the stable rates were 22.2 ％ (6/27) and 30.8 ％ (8/26),the decrease rates were 11.1％ (3/27) and 38.5 ％ (10/26).The remission rates of clinical sympotoms were 92.6 ％ (25/27) and 69.2 ％ (18/26) respectively in treatment group and control group.The difference of remission rate between two groups has no statistic significance (P ＞ 0.05),while the difference of the quality of life and clinical sympotoms between two groups were significant respectively (P ＜ 0.05).Conclusion The brucea javanica oil emulsion combined with the whole radiotherapy can relieve clinical sympotoms and improve the quality of life of patients,and may play a role on improving the effect of radiotherapy.
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Objective To study the short-term clinical efficacy of treating patients with advanced gastrointestinal cancer with lentinan injection and javanica oil emulsion injection.Methods Clinical information of 42 patients with advanced gastrointestinal cancer were retrospectively collected.The 42 patients were divided into two groups according to treatments,with 21 case in the control group who were treated with javanica oil emulsion injection,as well as 21 case in the treatment group treated with lentinan injection and javanica oil emulsion injection.The efficacy,quality of life (QOL) and adverse effects were observed after treatment for 3 weeks.Results 81.0％ (17/21)of patients in the treatment group improved in QOL,which was much higher than that in the control group 47.6％ ( 10/21 ) ( x2 =5.081,P =0.024 ).The objective remission rate was 19.0％ (4/21)and 14.3％ (3/21)in the treatment group and the control group respectively,with no significant differece bwtween the two groups( x2 =0.171,P =0.679 ).the disease control rate was 85.7％ (18/21)in the treatment group,which was significantly higher than that of 61.9％ (12/21)in the control group( x2 =4.200,P =0.040 ).The incidence of adverse effect related to hematological toxicity,liver and kidney function,the digestive tract and itching of skin were similar between the two groups (Ps ＞ 0.05 ).Phlebitis in the treatment group was not as frequent as that in the control group(P ＜0.05).Conclusion Treating patients with advanced gastrointestinal cancer with lentinan injection and javanica oil emulsion injection had high efficacy than treating only with javanica oil emulsion injection,and it improved QOL signifiantly with safety.
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Objective To evaluate the curative effects and side effects of burcea javanica oil emulsion(BJOE) in the treatment of pleural effusion of lung cancer by thoracic injection.Methods 40 cases with pleural effusion of lung cancer were treated by using BJOE.A dose of 50～100ml BJOE was injected intrapleurally,once every 5～7 days,4 time for a course of treatment,then the effects and side effects were observed after one month.Results The effective rate was 90%(36/40).The side effects were fever(n=4) and digestive sickness(n=2) as well thoracalgia(n=1).Conclusion Brucea javanica oil emulsion has good curative effect and low side effect in the treatment of pleural effusion of lung cancer.