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1.
李萍  姬白嫣  魏娟  杜小敬  黄凤 《肿瘤药学》2021,11(6):701-706
目的 探索藏红花素联合顺铂对人宫颈癌HeLa细胞的协同抑制作用及相关调控机制。方法 取对数生长期人宫颈癌HeLa细胞,设置空白对照组(DMSO)、藏红花素组(400 μg·mL-1)、顺铂组(5 μg·mL-1)、联合组(藏红花素400 μg·mL-1+顺铂5 μg·mL-1)。干预48 h后,CCK-8检测HeLa细胞增殖抑制率,采用CompuSyn软件计算藏红花素与顺铂的联合指数(CI),Annexin V-FITC染色法检测细胞凋亡,流式细胞术检测细胞周期分布,Western blotting检测激活型半胱氨酸天冬氨酸蛋白酶-3(Cleaved Caspase-3)、B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、细胞周期素D1(Cyclin D1)、周期蛋白依赖激酶2(CDK2)的表达。结果 与顺铂组比较,联合组细胞增殖抑制率显著升高(P<0.05),CI为0.68,具有中度协同效应;细胞凋亡率显著升高(P<0.01),G0/G1期细胞比例显著升高(P<0.05),而G2/M期比例显著降低(P<0.01),Cleaved Caspase-3、Bax蛋白表达水平及Bax/Bcl-2比值均显著升高(P<0.05),Cyclin D1、CDK2蛋白表达水平显著降低(P<0.01)。与空白对照组比较,藏红花素组G0/G1期细胞比例显著升高而G2/M期比例显著降低(P<0.01),Cleaved Caspase-3、Bax表达水平及Bax/Bcl-2比值均显著升高(P<0.01),Cyclin D1、CDK2表达水平显著降低(P<0.05)。结论 藏红花素联合顺铂可协同抑制人宫颈癌HeLa细胞的增殖和生长,其作用机制可能与调控凋亡相关蛋白的表达从而促进细胞凋亡、阻滞细胞周期进程有关。  相似文献   

2.
目的探讨大蒜素联合顺铂对人宫颈癌HeLa细胞增殖的抑制作用并探讨其机制。方法取对数生长期HeLa细胞,设对照组、大蒜素(50 μg/mL)组、顺铂(5 μg/mL)组、联合给药组(大蒜素50 μg/mL+顺铂5 μg/mL)。药物干预48 h后,通过MTT法检测细胞增殖抑制率,运用CompuSyn软件计算大蒜素与顺铂联合指数(CI),流式细胞术检测细胞周期分布和细胞凋亡水平,Western blotting法检测Cyclin D1、CDK2、P27、Cleaved Caspase-3、Bcl-2、Bax蛋白表达。结果与大蒜素组和顺铂组比较,联合给药组HeLa细胞增殖抑制率显著升高(P<0.05、0.01),CI为0.69(提示大蒜素与顺铂具有中度协同效应)。与对照组比较,大蒜素组和顺铂组G0/G1期细胞比例和细胞凋亡率显著升高(P<0.05、0.01),Cyclin D1、CDK2、Bcl-2表达显著下调且P27、Cleaved Caspase-3、Bax表达显著上调(P<0.05、0.01),Bax/Bcl-2比值显著升高(P<0.01)。与大蒜素组和顺铂组比较,联合给药组G0/G1期细胞比例和细胞凋亡率显著升高(P<0.05、0.01),Cyclin D1表达显著下调且P27、Cleaved Caspase-3、Bax表达显著上调(P<0.05、0.01),Bax/Bcl-2值显著升高(P<0.01)。结论大蒜素联合顺铂具有协同抑制人宫颈癌HeLa细胞增殖的作用,可能与调节细胞周期和凋亡相关蛋白表达,进而阻滞细胞周期进程并促进细胞凋亡有关。  相似文献   

3.
目的 观察紫花牡荆素(CAT)对人宫颈癌HeLa和SiHa细胞凋亡和侵袭转移的影响。方法 不同浓度CAT作用于HeLa和SiHa细胞不同时间后,采用MTT法观察药物对细胞活力的影响,流式细胞仪检测凋亡率,划痕试验观察细胞迁移率,基质胶法测定细胞粘附百分率,Transwell试验检测侵袭细胞数,Western blotting分析CAT对SiHa细胞抑制转移蛋白nm23-H1和促转移蛋白MTA1表达的影响。结果 CAT显著抑制HeLa和SiHa细胞活力,增加细胞凋亡率;降低细胞迁移百分率和黏附百分率;减少侵袭细胞数;明显增加SiHa细胞nm23-H1蛋白表达,降低MTA1蛋白表达。结论 CAT显著诱导人宫颈癌HeLa和SiHa细胞凋亡,抑制其侵袭迁移,提示其具有潜在的抗宫颈癌作用。  相似文献   

4.
人参皂苷Rg3对乳腺癌MCF-7细胞增殖和侵袭的影响   总被引:2,自引:1,他引:1  
目的 观察人参皂苷Rg3对雌激素受体阳性的乳腺癌细胞MCF-7增殖和侵袭的影响,并探讨其可能的作用机制。方法 采用MTT法检测细胞的增殖能力,流式细胞仪分析细胞周期分布以及凋亡比率,通过Transwell小室观察细胞侵袭力,RT-PCR法检测细胞中的MMP-9 mRNA的表达。结果 与对照组相比,人参皂苷Rg3能显著抑制MCF-7细胞的增殖;G0/G1期及S期细胞比例减少,而G2/M期细胞比例显著增加;同时细胞凋亡比率亦明显提升,而细胞侵袭指数降低,且呈现良好的剂量、时间依赖性。同时人参皂苷Rg3还能显著抑制细胞中MMP-9 mRNA的表达水平(P<0.05)。结论 人参皂苷Rg3能抑制MCF-7细胞的增殖和侵袭,其作用机制可能与其能降低MMP-9基因的表达有关。  相似文献   

5.
目的 制备高纯度3,5-O-二咖啡酰基奎宁酸,并评价其对人宫颈癌HeLa细胞的抗增殖活性。方法 采用柱色谱提取法和中压液相色谱法从奇蒿花中分离、纯化得到高纯度的3,5-O-二咖啡酰基奎宁酸。采用MTT法评价该化合物对人宫颈癌HeLa细胞的体外抗增殖活性。结果 柱色谱提取的提取率和中压液相色谱法的回收率分别为99.0%,61.2%,总回收率为54.0%。随着3,5-O-二咖啡酰基奎宁酸浓度升高,HeLa细胞存活率下降,细胞形态损伤增加,受试药物的IC50值为26.5µg·mL-1结论 本研究提供了一种简单、高效、节能的3,5-O-二咖啡酰基奎宁酸制备方法。3,5-O-二咖啡酰基奎宁酸对HeLa细胞具有一定的体外抗增殖活性。  相似文献   

6.
大黄素可能通过抑制Akt信号通路诱导HL-60细胞凋亡   总被引:1,自引:1,他引:1  
为研究大黄素(emodin)对人髓系白血病细胞株HL-60细胞增殖、凋亡的影响及Akt信号通路在其中的作用, 应用MTT法检测大黄素对HL-60细胞增殖的影响;细胞周期分析、线粒体细胞凋亡流式检测法分析细胞周期变化及细胞凋亡;Western blotting检测Akt信号通路蛋白表达水平的变化。结果显示,大黄素能有效抑制HL-60细胞的增殖,作用48 h的IC50约为20 μmol·L-1, 并能诱导其凋亡, 随药物作用浓度的增加, 凋亡率也逐渐上升; 大黄素作用后, HL-60细胞G0/G1期细胞增多, 而S期及G2期的细胞减少; Western blotting检测结果显示, 大黄素下调HL-60细胞Akt、p-Akt、IκB-α、p-IκB-α、p65、p-p65、mTOR及p-mTOR蛋白的表达。因此,大黄素能有效抑制HL-60细胞增殖,将细胞阻滞于G0/G1期,诱导其凋亡;Akt信号通路可能参与了大黄素抑制HL-60细胞增殖、诱导凋亡的过程。  相似文献   

7.
目的 探究甘草次酸对胃癌SGC7901细胞增殖、凋亡及PI3K-Akt-mTOR通路的影响。方法 体外培养胃癌SGC7901细胞,分为对照组和甘草次酸低、中、高浓度(12.5、25.0、50.0 μmol/L)组,药物处理24、48、72 h后,CCK-8法检测细胞增殖情况;药物处理48 h后,流式细胞仪检测细胞周期分布及细胞凋亡情况;Western blotting检测凋亡相关蛋白Bcl-2、Bax、cleaved Caspase-3以及PI3K-Akt-mTOR信号通路中磷酸化PI3K、Akt、mTOR蛋白表达水平。结果 甘草次酸低、中、高浓度组胃癌SGC7901细胞增殖受到明显抑制,并呈时间和剂量相关性(P<0.05)。与对照组比较,甘草次酸低、中、高浓度组胃癌SGC7901细胞G0/G1期细胞比例显著降低(P<0.05),G2/M期细胞比例及凋亡率显著升高(P<0.05),Bax、cleaved Caspase-3蛋白表达水平显著升高(P<0.05),Bcl-2、p-PI3K、p-Akt、p-mTOR蛋白表达水平显著降低(P<0.05)。结论 甘草次酸可抑制胃癌SGC7901细胞增殖,促进其凋亡,其机制可能与抑制PI3K-Akt-mTOR信号通路激活有关。  相似文献   

8.
目的 观察表没食子儿茶素没食子酸酯[(-)-epigallocatechin-3-gallate,EGCG]对人肺腺癌细胞株的凋亡诱导作用,探讨Ku70在EGCG促肺癌细胞凋亡中的作用机制。方法 构建pSliencer 4.1-CMV-shKu70质粒干扰Ku70的表达,建立细胞系;MTT法和Annexin V/PI双染色流式细胞术检测细胞的增殖及凋亡;Western blot法检测Bax、caspase-3(17 kDa)、Ku70蛋白的表达;免疫共沉淀法检测Ku70和Bax之间的相互作用。结果 EGCG可明显抑制A549的增殖(P<0.01),并诱导其凋亡(P<0.05),上调Bax、caspase-3表达,下调Ku70表达。抑制Ku70的表达后,EGCG对A549细胞的抑制增殖和促进凋亡作用更加明显,进一步显著上调caspase-3的表达(P<0.05),但是Bax的表达无明显变化;同时EGCG可以减弱Ku70-Bax之间的相互作用(P<0.05)。结论 EGCG可抑制人肺腺癌细胞增殖及诱导细胞凋亡,其机制与抑制Ku70的表达,抑制Ku70-Bax之间的相互作用,激活Bax,启动caspase级联反应有关。  相似文献   

9.
王军  董魁  张文娟  李静  张向梅 《肿瘤药学》2023,13(5):582-589
目的 探讨川芎嗪(TMP)对人结直肠癌SW480细胞增殖和凋亡的影响及其作用机制。方法 以DMSO(空白对照组)、不同浓度(50、100、200 μg·mL-1)的TMP和奥沙利铂(L-OHP,25 μg·mL-1)干预对数生长期人结直肠癌SW480细胞48 h。采用MTT法和EdU插入实验检测各组SW480细胞增殖率,细胞克隆实验观察SW480细胞克隆形成能力,流式细胞术、Western blotting检测细胞周期、凋亡和蛋白表达。结果 与空白对照组比较,经50、100、200 μg·mL-1的TMP或25 μg·mL-1的L-OHP干预可明显降低SW480细胞增殖率,提高细胞凋亡率;经100、200 μg·mL-1的TMP或25 μg·mL-1的L-OHP干预可明显抑制细胞克隆形成能力,阻滞细胞周期于G0/G1期,提高PTEN、Cleaved Caspase-3、Bax、P27表达量和Bax/Bcl-2比值,降低p-Akt、cyclin D1、Bcl-2表达量和Akt磷酸化率,差异均具有统计学意义(P<0.05)。与L-OHP 25 μg·mL-1组比较,经TMP 200 μg·mL-1干预能够明显降低SW480细胞增殖率、提高凋亡率,提高PTEN、Bax、P27表达量和Bax/Bcl-2比值,降低p-Akt、cyclin D1表达量和Akt磷酸化率,差异均具有统计学意义(P<0.05)。结论 TMP可能通过上调PTEN抑制PI3K/Akt通路,进而抑制SW480细胞增殖并促进其凋亡。  相似文献   

10.
目的 通过儿黄散白及胶双层膜(EHGBF)对人宫颈癌HeLa细胞增殖抑制及凋亡作用研究和急性毒性试验、皮肤刺激性试验、安全性试验,探讨其有效性和安全性。方法 采用MTT法考察不同浓度(0.1、1.0、5.0、10.0 mg/mL)的EHGBF、无白及胶儿黄散双层膜、白及胶双层膜及空白基质膜对HeLa细胞的增殖抑制作用;流式细胞术检测EHGBF对Hela细胞凋亡的影响;通过膜剂阴道给药大鼠急性毒性试验,对家兔完整皮肤及破损皮肤的刺激性试验,及对用药后家兔阴道取材肉眼观察及石蜡切片病理学观察,研究EHGBF对阴道刺激性。结果 空白基质膜对HeLa细胞无增殖抑制作用,EHGBF、白及胶双层膜、无白及胶儿黄散双层膜对HeLa细胞均发挥显著增殖抑制作用(P<0.05),作用强弱为EHGBF > 白及胶双层膜 > 无白及胶儿黄散双层膜;经过1、5、10 mg/mL浓度的EHGBF处理后,HeLa细胞凋亡率与对照组比较均显著升高(P<0.05);EHGBF在大剂量使用下无致死性,对皮肤及阴道几乎没有刺激性。结论 EHGBF可抑制人宫颈癌HeLa细胞增殖并促进其凋亡,无急性毒性,对皮肤无刺激性,对阴道黏膜几乎没有刺激性,安全性较好。  相似文献   

11.
New 2,6-piperidinediones 2a–g and 4a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides la–g or cycloalkylidenes 3a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5a–m. Some new selected compounds 2a–c,f, 4a–d & 5e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2f.  相似文献   

12.
Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10mgday−1) for 7 days. After this period dosage was doubled to 20mgday−1for the next 7 days and then again doubled to 40mgday−1, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.  相似文献   

13.
目的 建立鼻渊净胶囊的高效液相色谱(HPLC)指纹图谱.方法 采用Agilent SB-C18(4.6 mm×250 mm,5μm)色谱柱,乙腈-水为流动相、以1.0 ml/min流速行梯度洗脱,检测波长210 nm,柱温30℃,洗脱时间为80 min.采用中药色谱指纹图谱相似度评价系统(2004A版)对检测出色谱进行...  相似文献   

14.
Neuramide (NMD), a substance found in crude preparations of porcine stomach extract, is a viral inhibitor that also has putative immunostimulatory effects. The effects of NMD on stress-hormone (ACTH and prolactin—PRL) release were assessed inin vivoandin vitrostudies. In the former, blood levels of corticosterone and PRL were measured in NMD-treated male rats.In vitroexperiments were performed to evaluate the effects of NMD and three of its fractions (obtained with high performance liquid chromatography) on ACTH and PRL release from perfused rat pituitary slices. NMD increased plasma corticosterone levelsin vivoand produced dose-dependent increases inin vitropituitary release of ACTH. No effects on PRL secretion were observedin vivoorin vitro. The stimulatory effects on ACTH release were caused by the NMD fraction with a molecular weight of >5000<10000Da.  相似文献   

15.
In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.  相似文献   

16.
Inhibitory effects of the class III antiarrhythmic compound / -sotalol on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of both erythrocytes and the human caudate nucleus and on serum cholinesterase (ChE; EC 3.1.1.8) were studiedin vitrousing a spectrophotometric kinetic assay with acetylthiocholine (ASCh) as substrate. Sotalol concentrations in the assays varied from 0.32 to 3.2m . All isoenzymes studied were inhibited by / -sotalol in a reversible and concentration-dependent manner. Double reciprocal plots of the reaction velocity against varying ASCh concentrations revealed that / -sotalol reduced substrate affinity (apparent Michaelis constant, KM, increased) of serum ChE, but did not change the enzyme's maximal rate of ASCh hydrolysis (Vmax). Thus, / -sotalol inhibition of serum ChE was of the competitive type (rate constant for reversible competitive inhibition: Ki=0.51m ). In contrast, / sotalol reduced the maximal reaction velocity of the AChE isoenzyme from the central nervous system (caudate nucleus), but had no influence on substrate affinity of the enzyme (KMwith ASCh unchanged) indicating purely non-competitive inhibition kinetics (rate constant of reversible non-competitive inhibition: Ki′=0.44m ). / -sotalol inhibition of erythrocyte AChE was of mixed competitive/non-competitive type (Ki=0.31m , Ki′=0.49m ). Non-competitive / -sotalol inhibition of caudate nucleus AChE and the non-competitive component of erythrocyte AChE inhibition cannot be overcome by increased concentrations of the cholinergic transmitter acetylcholine (ACh). Peak / -sotalol plasma levels as described in the literature for both humans (15μ ) and experimental animals (dogs: 18μ ; rats: 260μ ) as well as maximal myocardial concentrations of the substance (dogs: 46μ ; rats: 478μ ) are in the range of about 2% to 100% of the sotalol inhibition rate constants determined in the present paper for cholinesterase isoenzymesin vitro. Thus, / -sotalol inhibition of ACh hydrolysisin vivomay contribute to both the well known antiarrhythmic potential and proarrhythmic side effects of the compound.  相似文献   

17.
Cyclosporine A, beside its current applications, possesses potential hepatoprotective effects. This study was directed to investigate the effect of Cyclosporine A pretreatment on hepatic injury due to carbon tetrachloride (CCl4) and -galactosamine. Rats were injected by two successive doses of Cyclosporine A (5mgkg−1day−1). Six hours after the second dose, 1mlkg−1of CCl4was administered i.p. Effects associated with Cyclosporine A pretreatment were examined by using isolated hepatocytes and hepatocytes that were immobilized and continuously perfused. -Galactosamine (5m ) was added directly to the perfusion medium. After isolation, hepatocytes were examined histologically by light and electron microscopy, immobilized and perfused for further metabolic functional activity evaluation. Cyclosporine A pretreatmentin vivoproduced hepatoameliorative effects of various degrees which were statistically significant as manifested by: (1) an increased trypan blue exclusion after CCl4; (2) an improved ureagenesis after CCl4; (3) a reduction in the lipid droplets accumulation in the cytoplasm produced by CCl4administration; (4) well preserved cytoplasmic organelles as mitochondria, endoplasmic reticulum ER, nuclear chromatin structures that were altered by CCl4; and (5) an increased hepatocytes survival in the agarose gel matrix, reduction of LD leakage and improvement of ureagenesis after -galactosamine addition to the perfusion medium. The beneficial effect of Cyclosporine A pretreatment in modifying hepatotoxicity of chemical insults merits further studies.  相似文献   

18.
喙果黑面神化学成分研究   总被引:2,自引:0,他引:2  
目的研究大戟科植物喙果黑面神(Breynia rostrata Merr.)的化学成分。方法利用硅胶、凝胶等色谱技术分离纯化化学成分,根据化合物的理化性质和光谱数据进行结构鉴定。结果从喙果黑面神的正丁醇萃取部分分离得到4个化合物,分别鉴定为6-O-甲基丙酰基-α-D-吡喃葡糖(6-O-methylpropanoyl-α-D-glucopyranose,1);4″-苯酚基-6-O-甲基丙酰基-β-D-吡喃葡糖苷(4″-phenolic-6-O-methylpropanoyl-β-D-glucopyranoside,2);1-O-没食子酰基-β-D-吡喃葡糖苷(1-O-galloyl-β-D-glucopyranoside,3);熊果苷(arbutin,4)。结论化合物1和2为新化合物,3和4均为首次从该种植物分离得到。  相似文献   

19.
In this study 2-guanidine-4-methylquinazoline (2-GMQ) appeared to decrease basal and stimulated gastric acid secretion, while structurally related compounds as dimethyl- biguanide, cyanoguanidine and 2-cyanoamino-4-methylpyrymidine did not. Thus, there is an antisecretory effect when the biguanide group is associated with a lipophilic structure. The antisecretive effects exerted by 2-GMQ are associated with anti H2-histamine activity.The anti H2-histamine nature of the effects of 2-GMQ was confirmed by the capacity of this compound of depressing the chronotropic activity of the isolated guinea pig auricle increased by histamine, as well as relaxant activity in rat uterus contracted by histamine, since both preparations are rich in H2-histamine receptors.  相似文献   

20.
穆向荣  林林  焦阳  林永强 《药学研究》2019,38(7):419-423
瓜蒌子、瓜蒌皮、瓜蒌、天花粉来源于栝楼的不同药用部位,4味药材均为常用的大宗药材,现行版《中国药典》对其制定的质量标准过于简单,无法科学合理地控制其质量。本文对瓜蒌子、瓜蒌皮、瓜蒌、天花粉安全性和有效组分的研究进行综述,明确了相关研究存在的问题并针对问题提出建议,为科学全面的药材及饮片标准的制定提供参考依据。  相似文献   

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