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1.
化合物YSY-01A是一种新合成的蛋白酶体抑制剂,前期研究已经证实其具有良好的抑制肿瘤增殖作用。但是其作用机制尤其是对细胞周期的阻滞作用仍不清楚。本实验旨在评价YSY-01A的抗肿瘤作用与细胞周期阻滞的关系,并探讨可能的分子机制。实验结果证实,YSY-01A能够显著抑制大肠腺癌细胞HT-29的增殖(P<0.05),且具有浓度和时间依赖性。进一步实验表明,YSY-01A能够把HT-29细胞阻滞在G2/M转换点上,显著地上调cyclinB1,Wee1,p-cdc2(Tyr15)及p53,p21,p27蛋白的表达(P<0.05)。当YSY-01A浓度高于0.5μM时,HT-29会显示出典型的细胞毒症状,差异具有显著性(P<0.05);而本文用于机制研究的药物浓度均低于此值。总之,YSY-01A对HT-29细胞具有显著的增殖抑制作用,其分子机制与G2/M转换点阻滞有关。 相似文献
2.
《齐鲁药事》2015,(8)
目的通过观察白藜芦醇对结肠癌细胞系HT-29增殖的影响并检测程序性细胞死亡4蛋白表达水平,探讨白藜芦醇的抗结肠癌增殖作用及部分相关机制。方法 HT-29细胞经不同浓度白藜芦醇作用后,流式细胞术检测细胞周期分布及凋亡情况,Western blot法检测程序性细胞死亡4蛋白表达水平变化。结果不同浓度的白藜芦醇对HT-29细胞的增殖有抑制作用,并且呈现出一定的剂量依赖性(P<0.01),白藜芦醇改变细胞周期分布,细胞周期阻滞在S期,同时诱导HT-29细胞凋亡,试验组与空白对照组相比,S期细胞比例及凋亡率明显增高(P<0.05),细胞周期被阻滞,增殖抑制。白藜芦醇处理后HT-29细胞程序性细胞死亡4蛋白表达水平上调,与对照组比较,差异有统计学意义(P<0.01)。结论白藜芦醇能够显著抑制HT-29细胞株的增殖,细胞周期阻滞于S期,诱导肿瘤细胞凋亡,其肿瘤抑制作用可能与程序性细胞死亡4蛋白表达上调有关。 相似文献
3.
二烯丙基二硫对人结肠癌HT-29细胞G_1期的阻滞作用 总被引:1,自引:2,他引:1
目的探讨二烯丙基二硫(DADS)对人结肠癌HT-29细胞G1期的阻滞作用及分子机制。方法采用MTT、细胞计数法、流式细胞术和免疫细胞化学方法分析DADS对体外培养的HT-29细胞增殖抑制作用、细胞周期分布及细胞周期相关蛋白表达的影响。结果MTT法显示,60、120μmol.L-1DADS作用HT-29细胞24 h后,生长抑制率分别达23.1%、45.6%。细胞计数法表明,常规培养HT-29细胞群体倍增时间为22.58 h,60μmol.L-1DADS作用HT-29细胞后,其细胞群体倍增时间延长到31.20 h。流式细胞仪分析结果显示,60μmol.L-1DADS阻滞HT-29细胞在G1期,与对照组相比,可使G1期细胞增加约2倍,而120μmol.L-1DADS显著地将细胞阻滞在G2/M期。免疫细胞化学分析表明在G1期阻滞同时有p21W af1蛋白表达上调,Cyc lin E、C-myc蛋白表达下降。结论低剂量DADS对HT-29细胞的抑制增殖作用可能与G1期阻滞有关,DADS对HT-29细胞G1期阻滞的分子机制可能与调节p21W af1、Cyc lin E、C-myc表达相关。 相似文献
4.
异甘草素对人宫颈癌细胞增殖的抑制作用 总被引:2,自引:1,他引:2
目的鉴于异甘草素(ISL)对不同肿瘤细胞系的不同作用,研究ISL对人宫颈鳞状上皮癌细胞(CaSki)癌细胞的影响及有关机制。方法体外研究采用MTT法测定细胞增殖;流式细胞仪检测细胞周期;逆转录聚合酶链反应(RT-PCR)分析细胞周期蛋白B1(cyclin B1)mRNA表达;Western免疫印迹分析cyclin B1,P34cdc2和磷酸化P34cdc2(phospho-cdc2,酪氨酸15)蛋白表达;体内研究通过建立人宫颈癌CaSki细胞裸鼠移植瘤模型观察抑瘤率。结果ISL浓度依赖性(10~80μmol.L-1)抑制CaSki细胞增殖,IC50为(19.3±3.3)μmol.L-1,且呈时间依赖性。ISL 20μmol.L-1作用3 d对细胞抑制率为82.3%;ISL浓度依赖性(10~80μmol.L-1)干扰CaSki细胞周期,细胞周期阻滞于S和G2/M期,S和G2/M期的百分率分别从23.1%和8.2%上升到43.2%和32.1%;同时G0/G1期细胞百分率从68.7%下降到24.7%;RT-PCR分析显示,ISL(10~80μmol.L-1)显著抑制cyclin B1 mRNA表达,抑制率最高可达61.7%,且呈时间依赖性;Western免疫印迹分析显示,ISL作用24 h cyclin B1蛋白表达开始不同程度下降,48 h下降明显,P34cdc2变化较小,ISL作用16 h后磷酸化P34cdc2(酪氨酸15)蛋白水平明显改变;ISL(20~500 mg.kg-1.d-1)剂量依赖性抑制CaSki细胞裸鼠皮下移植瘤的生长,抑瘤率分别为36.8%,51.2%和84.6%,且对动物体重和外周血白细胞数均无明显影响。结论ISL可以显著抑制人宫颈癌细胞体内外增殖,其机制与将细胞周期阻滞于S和G2/M期及影响细胞周期因子cyclin B1的表达和改变P34cdc2的磷酸化水平有关。 相似文献
5.
4-氨基-2-三氟甲基苯基维甲酸酯对K562细胞分化和细胞周期的影响 总被引:3,自引:0,他引:3
目的本研究探讨新型维甲酸衍生物4-氨基-2-三氟甲基苯基维甲酸酯(4-amino-2-trifluoromethyl-phenyl retinate,ATPR)对K562细胞株的抑制增殖和诱导分化活性并对其机制进行研究。方法ATPR作用于K562细胞3d后,通过MTT法检测细胞的增殖,NBT还原实验法分析细胞的分化指标,瑞氏染色法在油镜下观察加药前后细胞形态学变化,FCM检测分析细胞周期,RT-PCR法检测cyclinE、cyclinD1、CDK2、CDK4、CDK6、p21cip1、p27kip1、p57kip2和PCNA mRNA的变化情况。Western blot法检测cyclin D1和CDK4蛋白表达的改变。结果ATPR呈浓度依赖性抑制K562细胞增殖的作用。ATPR诱导分化活性表现为NBT阳性细胞率增加,油镜下观察K562细胞有分化成熟的改变,G0/G1期细胞表达量增加,S期细胞表达量减少,呈G1期阻滞。RT-PCR检测发现cyclin E、cyclin D1、CDK2、CDK4、CDK6表达减少,PC-NA、P21cip1、P27kip1改变不明显,P57kip2表达增加。Western blot检测cyclin D1和CDK4蛋白表达减少。结论ATPR有较强的抑制K562细胞增殖并诱导其分化的活性,并通过上调P57kip2的表达,抑制Cyclin-CDK激酶复合物,发挥细胞周期阻滞的作用。 相似文献
6.
紫杉醇对U373细胞周期阻滞及增殖抑制的机制研究 总被引:1,自引:1,他引:1
目的研究紫杉醇(PTX)诱发神经胶质瘤U373细胞的周期阻滞和增殖抑制的相关机制。方法 MTT检测细胞增殖抑制率,流式细胞术检测细胞周期分布,免疫细胞荧光化学观察细胞形态学变化,RT-PCR和Western blot检测细胞周期相关CyclinB1、CyclinD1、CDK1、CDK2和p53的表达变化。结果 PTX可以明显抑制U373细胞的增殖活性,抑制作用呈时间浓度依赖性;细胞周期分析显示,实验组细胞G2/M期比例增高;细胞免疫荧光检测实验组细胞阻滞于有丝分裂期;RT-PCR和Western blot显示,PTX可以增加CDK1和CyclinB1表达,降低CyclinD1表达(P<0.05),而对CDK2无明显影响。结论 PTX能够抑制神经胶质瘤U373细胞增殖,引起有丝分裂期阻滞,诱导细胞凋亡,与其细胞周期相关蛋白表达水平密切相关。 相似文献
7.
化合物YSY-01A是一种新型蛋白酶体抑制剂,前期研究已初步证实其具有显著的抗肿瘤作用,但是该化合物对人胃癌细胞的作用及相关机制研究尚不明确。本实验旨在评价化合物YSY-01A对人胃癌细胞MGC-803的体外和体内作用,并探讨可能的分子机制。体外研究表明,化合物YSY-01A对人胃癌细胞MGC-803具有显著的增殖抑制作用?体内研究表明,化合物YSY-01A单用及与5-FU联用时均可以显著地抑制裸鼠MGC-803异种移植瘤的生长,并且化合物YSY-01A与5-FU具有协同作用。分子机制研究证实,YSY-01A可以显著地抑制TNF-α和IFN诱导的NF-κB核转位,显著地下调IKK-β、IL-1β、iNOS蛋白的表达和上调COX-2蛋白的表达。综上所述,化合物YSY-01A具有较好的抗肿瘤作用,其机制与NF-κB通路相关蛋白有关。 相似文献
8.
目的:探讨喜树碱类衍生物与celecoxib联合用药的体外和体内的抗肿瘤作用及机制,同时观察celecoxib对Irinotecan(CPT-11)引起裸鼠腹泻的影响。方法:以MTT法检测结肠癌细胞系在联合应用celecoxib后对喜树碱及其衍生物的化学敏感性的改变;流式细胞术检测celecoxib与喜树碱联合用药后HT-29细胞的凋亡比率和细胞周期的变化;WesternBlot法检测环氧合酶-2(COX-2)以及凋亡相关蛋白(Bcl-2、Caspase-3、P53)的表达。以HT-29细胞裸鼠移植瘤模型观察celecoxib与CPT-11联合应用的体内抗肿瘤作用,并且观察celecoxib对CPT-11引起腹泻及体重减轻的影响。 相似文献
9.
细胞周期(cell cycle)是指细胞从上一次有丝分裂结束到下一次有丝分裂完成的整个过程。一个完整的细胞周期包括G1期、S期、G2期和M期。细胞周期的有序运行主要依赖于cyclin/细胞周期蛋白依赖性激酶(CDK)复合物的表达。细胞周期蛋白(cyclin)、CDK的异常表达,CDK抑制蛋白的缺失都会导致细胞周期紊乱,细胞增殖失控,发生癌变。近年来的研究证实,Rb蛋白家族是细胞周期的“开关”,Rb蛋白被细胞周期蛋白依赖性激酶(CDKs)磷酸化后,细胞才能分化增殖。 相似文献
10.
目的 研究EBF1基因下调对肺腺癌A549细胞体内外增殖的影响,并初步探讨其机制。方法 通过免疫组化和RT-PCR检测EBF1在肺癌组织和肺癌细胞系中的表达情况。根据本实验室设计的针对EBF1的小干扰RNA(shRNA)序列,选择一条已经证实最有效的序列作为靶序列和一条随机序列作为阴性对照,构建重组逆转录病毒shRNA表达载体并将其转染入A549细胞中;应用RT-PCR和蛋白质印迹法(Western blot)检测对EBF1基因的沉默效果;应用MTT比色法及BrdU染色法实验检测EBF1-shRNA对A549细胞体外增殖的影响;利用Transwell实验及划痕实验检测EBF1-shRNA对A549细胞体外侵袭及迁移能力的影响;利用流式细胞仪分析各组细胞的细胞周期;通过裸鼠腋窝皮下接种各组细胞,观察EBF1-shRNA对A549细胞在裸鼠体内的致瘤能力的影响;Western blot检测CDK6、P21、P27蛋白表达。结果 EBF1在癌旁组织及肺癌组织中的基质细胞中不表达,在NSCLC及SCLC癌细胞细胞核中表达。EBF1-shRNA有效地沉默了EBF1基因mRNA和蛋白的表达;沉默EBF1基因的表达能够抑制A549细胞的体内外增殖能力,使实验组细胞的细胞周期阻滞于G 1 期;沉默EBF1基因的表达后,实验组细胞中CDK6蛋白表达降低,P21、P27蛋白增加。结论 EBF1-shRNA通过使细胞周期阻滞于G 1 期来抑制肺腺癌A549的体内外增殖能力,这种抑制作用涉及CDK6表达下降以及P21/P27的表达上调。 相似文献
11.
Pevarello P Brasca MG Orsini P Traquandi G Longo A Nesi M Orzi F Piutti C Sansonna P Varasi M Cameron A Vulpetti A Roletto F Alzani R Ciomei M Albanese C Pastori W Marsiglio A Pesenti E Fiorentini F Bischoff JR Mercurio C 《Journal of medicinal chemistry》2005,48(8):2944-2956
Inhibitors of cyclin-dependent kinases (CDK) such as CDK2/cyclin A-E are currently undergoing clinical trials to verify their potential as new anticancer agents. In a previous article we described the lead discovery process of a 3-aminopyrazole class of CDK2/cyclin A-E inhibitors. The endpoint of this process was PNU-292137, a compound endowed with in vivo antitumor activity in a mouse tumor xenograft model. We optimized this lead compound to improve some physicochemical properties, notably solubility and plasma protein binding. This lead optimization process brought us to the discovery of (2S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[4-(2-oxo-1-pyrrolidinyl)phenyl]propanamide (PHA-533533, 13), a compound with a balanced activity vs druglike profile. Compound 13 inhibited CDK2/cyclin A with a K(i) of 31 nM, counteracting tumor cell proliferation of different cell lines with an IC(50) in the submicromolar range. Solubility was improved more than 10 times over the starting lead, while plasma protein binding was decreased from 99% to 74%. With exploitation of this globally enhanced in vitro profile, 13 was more active than PNU-292137 in vivo in the A2780 xenograft model showing a tumor growth inhibition of 70%. Proof of mechanism of action was obtained in vivo by immunohistochemical analysis of tumor slices of 13-treated vs untreated animals. 相似文献
12.
Pevarello P Brasca MG Amici R Orsini P Traquandi G Corti L Piutti C Sansonna P Villa M Pierce BS Pulici M Giordano P Martina K Fritzen EL Nugent RA Casale E Cameron A Ciomei M Roletto F Isacchi A Fogliatto G Pesenti E Pastori W Marsiglio A Leach KL Clare PM Fiorentini F Varasi M Vulpetti A Warpehoski MA 《Journal of medicinal chemistry》2004,47(13):3367-3380
Abnormal proliferation mediated by disruption of the normal cell cycle mechanisms is a hallmark of virtually all cancer cells. Compounds targeting complexes between cyclin-dependent kinases (CDK) and cyclins, such as CDK2/cyclin A and CDK2/cyclin E, and inhibiting their kinase activity are regarded as promising antitumor agents to complement the existing therapies. From a high-throughput screening effort, we identified a new class of CDK2/cyclin A/E inhibitors. The hit-to-lead expansion of this class is described. X-ray crystallographic data of early compounds in this series, as well as in vitro testing funneled for rapidly achieving in vivo efficacy, led to a nanomolar inhibitor of CDK2/cyclin A (N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(2-naphthyl)acetamide (41), PNU-292137, IC50 = 37 nM) with in vivo antitumor activity (TGI > 50%) in a mouse xenograft model at a dose devoid of toxic effects. 相似文献
13.
《中国药理学与毒理学杂志》2019,(9)
OBJECTIVE To investigate the inhibitory effect of scutellarin on the self-renewal and differentiation of HT-29 cells-derived cancer stem-like cells(HT-29 CSC) in vitro and in vivo, and to explore its mechanism. METHODS The effect of scutellarin on the growth of HT-29 CSC was determined by 3 D Culture assay. The effect of scutellarin on growth and transformation of HT-29 CSC was probed by soft agar colony formation assay. The effect of scutellarin on the differentiation of HT-29 CSC was determined by serum induction differentiation assay in vitro. The effects of scutellarin on the expressions of marker gene Lgr5, target gene c-Myc, proliferation gene CK20 and Nanog gene were measured by quantitative real-time RT-PCR. Investigate the effect of scutellarin on the expression of c-Myc, Gli1, and Lgr5 protein by Western blotting. A subcutaneous xenograft model of colon cancer in nude mice was established and administered by intraperitoneal injection. The change of body weight and tumor size of nude mice were observed every two days. Investigate the effects of scutellarin on the growth of xenograft tumors in nude mice. The expression of CD133, Lgr5, Gli1,Ptch1, c-Myc, Ki67, CK20, Nanog gene in tumors were measured by quantitative real-time RT-PCR. The expression of c-Myc, Gli1, Lgr5, CD133, Ki67 protein were measured by Western blotting. RESULTS Scutellarin can inhibit the growth of HT-29 CSC in 3 D culture. Compared with the solvent control group, scutellarin can significantly inhibit the growth and transformation and differentiation of HT-29 CSC in vitro(P<0.01). The expression levels of marker genes Lgr5, target gene c-Myc, proliferation gene CK20 and Nanog in HT-29 CSC were down-regulated by scutellarin. Scutellarin can reduce the expression of c-Myc, Gli1, and Lgr5 protein in HT-29 CSC.Scutellarin can inhibit the growth of colon cancer xenografts, lower CD133, Lgr5, Gli1, Ptch1, c-Myc, Ki67, CK20, and Nanog mRNA level of xenograft tumors, reduce the expression of c-Myc, Gli1, Lgr5, CD133, and Ki67 protein of xenograft tumors in nude mice. CONCLUSION Scutellarin,which is the main component of scutellaria barbata, can inhibit the differentiation of HT-29 CSC and the mechanism is to inhibit the activity of Hedgehog signaling pathway. 相似文献
14.
A newly synthesized dithiocarbamate derivative, 4-methylpiperazine-1-carbodithioc-acid-3-cyano-3,3-diphenylpropyl ester hydrochloride (TM208), has demonstrated anticancer effects with low toxicity in earlier studies; however, the mechanism has yet to be identified. We explored antitumor effects of TM208 and the possible mechanisms by which it inhibited the growth of human hepatocellular carcinoma cell line QGY-7703 xenograft tumors. Cell proliferation was evaluated with the sulforhodamine B assay in vitro. The results suggested that TM208 had slightly antiproliferative activity on QGY-7703 cells. The antitumor effect of TM208 was assessed in nude mice xenografted with QGY-7703 tumors. We found that TM208 significantly inhibited tumor growth but did not cause loss of body weight or leukocytopenia. Western blotting was used to detect the expression of protein kinase C alpha, mitogen-activated protein kinase signal pathways, and cell cycle-related proteins. The results showed that TM208 decreased the expression of protein kinase C alpha, phospho-extracellular signal-regulated kinase-1/2, phospho-p38, cyclin B1, cell division cycle 2 (cdc2), and phospho-cdc2 (Thr161) and increased the expression of phospho-cdc2 (Tyr15). Taken together, our data show that TM208 has little antiproliferative effect on QGY-7703 cells in vitro, whereas it significantly inhibits the growth of QGY-7703 xenograft tumors with low toxicity in vivo. The inhibition of mitogen-activated protein kinase signal pathways and the regulation of the G2/M phase may be responsible for its antitumor effects. 相似文献
15.
B Stefańska M Dzieduszycka M M Bontemps-Gracz E Borowski S Martelli R Supino G Pratesi M De Cesare F Zunino H Ku?nierczyk C Radzikowski 《Journal of medicinal chemistry》1999,42(18):3494-3501
The synthesis of dihydroxybenzoperimidine derivatives, which are chromophore-modified dihydroxyanthracenediones with an additional pyrimidine ring incorporated into the chromophore, is reported. These derivatives are structurally related to the antitumor agent mitoxantrone. Their synthesis was carried out by the reaction of 6-amino-8,11-dihydroxy-7H-benzo[e]perimidin-7-one (5) or 6,8, 11-trihydroxy-7H-benzo[e]perimidin-7-one (10) with a number of respective (alkylamino)alkylamines. The dihydroxybenzoperimidine derivatives exhibited in vitro cytotoxic activity against murine leukemia L1210 and human leukemia HL60 cell lines comparable to that of mitoxantrone. These compounds also exhibited a range of in vitro activity against the human MDR-type resistant leukemia K562R cell line with the MDR phenotype. The most active compound of this series, namely 6a, exhibited potent in vitro cytotoxic activity against a panel of human cell lines. Furthermore, in contrast to both mitoxantrone and doxorubicin, it displayed little cross-resistance in cell lines characterized by a MDR phenotype. Cell cycle analysis in the sensitive HT-29 and mitoxantrone-resistant HT-29/Mx (not identified resistance mechanism) cell lines has revealed that both mitoxantrone and 6a induce a G2/M block. However, while the proportion of apoptotic cells after mitoxantrone treatment is similar for both sensitive and resistant cell lines, it is much lower for 6a. Compound 6a tested against P388 murine leukemia in vivo displayed a significant antitumor effect (%T/C 196 at an optimal dose of 10 mg/kg). The property of overcoming the cross-resistance was maintained also in in vivo efficacy studies, where no difference was observed in the antitumor activity of compound 6a against the A2780 human tumor xenograft and its MDR A2780/Dx subline. We conclude that benzoperimidines, if properly substituted, constitute a novel class of compounds that can overcome multidrug resistance. 相似文献
16.
Anticancer effects of the Chinese medicine matrine on murine hepatocellular carcinoma cells 总被引:2,自引:0,他引:2
Matrine is a component of the traditional Chinese medical herb Sophora flavescens Ait, which is widely used to treat diseases such as viral hepatitis, cardiac arrhythmia and skin inflammations. As indicated by previous reports, the molecular mechanism of matrine's anti-cancer effect has been poorly clarified. In this study, we used both in vitro and in vivo models to investigate matrine's antitumor effect and its possible molecular mechanisms. Murine hepatocellular carcinoma H22 cells were cultured in the presence of matrine at various concentrations (0.2 - 2.0 mg/mL). A dose-dependent antiproliferation effect was observed. The 50 % inhibitory concentration (IC (50)) was 0.6 mg/mL. Antiproliferation effects of matrine were associated with an increase in cells arrested in the G (1) phase of the cell cycle. Morphological changes, flow cytometric analysis and expression of the proapoptotic protein Bax indicated that this anticancer effect was mediated via apoptosis. In vivo antitumor efficacy was evaluated following S. C. inoculation of H22 cells in BALB/c mice. Matrine administrated I. P. resulted in strong in vivo anticancer activity. Our results showed that seven doses of matrine at 50 mg/kg/dose inhibited 60.7 % of tumor growth. Transmission electron microscope (TEM) analysis and histoimmunochemical staining for Bcl-2 and Bax proteins also indicated induction of apoptosis in tumor tissues by matrine. Taken together, our results demonstrate that matrine possesses strong antitumor activities in vitro and in vivo. Inhibition of cell proliferation and induction of apoptosis are the likely mechanisms responsible for matrine's antitumor activities. 相似文献
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Lin R Connolly PJ Huang S Wetter SK Lu Y Murray WV Emanuel SL Gruninger RH Fuentes-Pesquera AR Rugg CA Middleton SA Jolliffe LK 《Journal of medicinal chemistry》2005,48(13):4208-4211
A series of 1-acyl-1H-[1,2,4]triazole-3,5-diamine analogues were synthesized as cyclin-dependent kinase (CDK) inhibitors. These compounds showed potent and selective CDK1 and CDK2 inhibitory activities and inhibited in vitro cellular proliferation in various human tumor cells. Representative compound 3b demonstrated in vivo efficacy in a human melanoma A375 xenograft model in nude mice. 相似文献
19.
To survey the immune regulatory function of recombinant human prolactin (rhPRL) and its potential application in adoptive immunotherapy, CB17-SCID mice were loaded with human colon adenocarcinoma HT-29 cells (5 x 10(5) cells/mouse, i.p.) 24 h before adoptive transfer with the purified human NK cells followed by rhPRL injection (10 mug/mouse, every other day for a total of 10 injections). Upon analysis, rhPRL did not exert any direct inhibitory effects on HT-29 cells but slightly improved the tumor cell growth both in vitro and in vivo. After SCID mice were reconstituted with human NK cells, rhPRL improved the antitumor effects of human NK cells in HT-29-bearing SCID mice, showing a prolonged survival from 70.4 to 112.1 days, and the increased survival rate from all died to 40% survival for more than 160 days. rhPRL improved the proliferation of human NK cells with or without PHA stimulation. rhPRL also directly enhanced the cytotoxicity of human NK cells against HT-29 tumor cells in 4-h coculture. The supernatant of rhPRL-stimulating NK cells inhibited the proliferation of HT-29 cells through, at least partly, the interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatant. Thus, rhPRL administration in HT-29 tumor-bearing SCID mice promotes the antitumor effects of adoptively transferred NK cells. 相似文献
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目的对SHR115723进行初步体外和体内药效学、药动学研究,并与舒尼替尼进行比较,以了解SHR115723新药开发的潜力。方法用磺酰罗丹明B蛋白染色法检测药物对人脐静脉内皮细胞体外生长的抑制作用,用裸小鼠异体移植入结肠癌HT-29模型检测药物体内的抗肿瘤作用,应用高效液相色谱-紫外检测法进行大鼠体内的药动学研究。结果SHR115723和舒尼替尼对人脐静脉内皮细胞增殖的IC_(50)分别为(1.3±s 0.3)和(0.78±0.23)μmol·L~(-1)。SHR115723和舒尼替尼对裸小鼠异体移植人结肠癌HT-29生长具有明显的抑制作用。SHR115723的AUC和c_(max)高于舒尼替尼,但V_d较小。结论SHR115723具有明显的抗肿瘤作用,具有一定的新药开发潜力。 相似文献