地塞米松预处理人乳腺癌MCF-7细胞对多西他赛抗肿瘤活性的影响

目的 探讨地塞米松预处理人乳腺癌MCF-7细胞后,对化疗药物多西他赛(艾素)抗肿瘤活性的影响.方法 以不同浓度(1×10-8～1×10-6 mol·L-1)的地塞米松预先作用于人乳腺癌MCF-7细胞后,再以艾素(5×10-6 mol·L-1)处理,在以上药物作用的相应时间段,通过流式细胞仪技术测定细胞凋亡,采用细胞计数观察细胞生长密度、形态.结果 地塞米松对MCF-7细胞增殖有抑制作用(P＜0.01),艾素能够明显抑制MCF-7细胞增殖,促进其凋亡(P＜0.01),地塞米松预处理后艾素干预MCF-7细胞的增殖抑制作用较单用艾素减弱(P＜0.01),且随地塞米松浓度的增加,其对化疗药艾素的凋亡抑制作用的影响增强.结论 地塞米松预处理对艾素诱导的人乳腺癌MCF-7细胞的凋亡具有明显的阻抑作用,抑制了多西他赛的抗肿瘤活性.     

雷公藤甲素对ERα蛋白介导的人乳腺癌MCF-7细胞增殖抑制的影响

目的：研究雷公藤甲素对激素依赖性人乳腺癌细胞MCF-7增殖的抑制作用及可能的机制。方法：MTT法检测雷公藤甲素对MCF-7细胞增殖的抑制作用,Hoechst染色法检测其对细胞凋亡的影响,Western blotting法观察雷公藤甲素对雌激素受体（ER）α蛋白表达的影响。结果：雷公藤甲素对MCF-7细胞增殖有显著的抑制作用,并且呈现良好的时效和量效关系,雷公藤甲素能有效诱导MCF-7细胞凋亡,并且对ERα具有明显的下调作用。结论：雷公藤甲素能抑制人乳腺癌细胞MCF-7增殖并且诱导其凋亡,其诱导MCF-7细胞凋亡的作用机制可能与其下调ERα的表达有关。     

姜黄素诱导乳腺癌MCF-7细胞凋亡

目的 研究姜黄素对人乳腺癌细胞株MCF-7细胞增殖抑制和诱导凋亡作用.方法 MTT法检测姜黄素对MCF-7细胞的增殖抑制作用;流式细胞术(FCM)PI单染检测细胞周期;Annexin V/PI双染法检测细胞凋亡;Western blot法检测Bcl-2和Bax蛋白的表达.结果 姜黄素对MCF-7细胞生长有明显抑制作用,并呈剂量、时间依赖性;姜黄素能使MCF-7细胞阻滞在G1/S期,可以诱导细胞凋亡,Bax蛋白表达上调,而Bcl-2的表达减少.结论 姜黄素对人乳腺癌MCF-7细胞的增殖具有显著的抑制作用并可诱导细胞凋亡.其分子作用机制可能与其上调Bax基因表达水平的同时下调Bcl-2基因表达水平,从而诱导细胞凋亡有关.     

硫酸乙酰肝素多糖类似物的抗乳腺癌活性研究进展*

硫酸乙酰肝素（heparan sulfate，HS）参与乳腺癌发生和发展的多个环节，随着HS对细胞生长因子调节机制研究的深入，HS多糖类似物的研发已经成为当前研究的热点。现综述HS结构及在乳腺癌发生发展中的作用和机制、HS多糖类似物的分类、天然产物中提取的多糖和化学修饰的多糖衍生物的抗癌活性及构效关系的研究进展。     

Homopterocarpanes as bridged triarylethylene analogues: synthesis and antagonistic effects in human MCF-7 breast cancer cells

A series of new compounds structurally derived from 6a,12a-dihydro-6H,7H-[1]-benzopyran-[4,3-b]-benzopyran (homopterocarpane) was efficiently synthesized by reduction of the corresponding pyrilium salts obtained by treatment of selected flavanones and aldehydes with anhydrous HClO4. Cytotoxic effects on the human breast cancer cell line MCF-7 and antiestrogenic activity (only for compounds which resulted more active than tamoxifen (TAM)) on MCF-7 cells stimulated by 17beta-estradiol were evaluated. In vivo antiestrogenic activity and the relative binding affinity were also assessed. Some of the new compounds (4c, 4h, 4i and 4l) showed a biological activity in the micromolar range, and were more potent than TAM taken as the reference.     

Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by oridonin nanosuspension

The mechanism for anti-tumor activity of oridonin (ORI) nanosuspension, prepared by the high pressure homogenization method, was studied using MCF-7 human breast carcinoma cells in vitro. MTT assay, observation of morphologic changes, flow cytometric analysis, and western blot analysis indicated that ORI nanosuspension could significantly intensify the in vitro anti-tumor activity to MCF-7 cells, as compared with ORI solution. Furthermore, ORI nanosuspension induced G₂/M stage proliferation arrest and apoptosis in MCF-7 cells depending on its concentration. In addition, western blot analysis indicated that the pro-caspase-3 protein was not cleaved into the activated form and the expression of anti-apoptotic Bcl-2 protein decreased, on the contrary, the expression of pro-apoptotic Bax protein increased in a dose-dependent manner in ORI nanosuspension-treated cells. These observations indicated that the anti-tumor activity of ORI nanosuspension was intensified by cell-cycle arrest and apoptosis induction.     

Synthesis and biological evaluation of resveratrol derivatives with anti-breast cancer activity

Resveratrol is a natural phytoestrogen produced by plants to protect themselves from injury, UV irradiation, and fungal attack. The main active structure is E-resveratrol, which has many pharmacological activities. As the structure of resveratrol is similar to the natural estrogen 17β-estradiol and the synthetic estrogen E-diethylstilbestrol, resveratrol is used in reducing the incidence of breast cancer. However, the therapeutic application of resveratrol is limited due to its low bioavailability. To improve its bioavailability and pharmacological activity, some resveratrol derivatives have been designed and synthesized by substitutions of methoxy, hydroxyl, and other functional groups or heterocyclic esterification either on the “A” or “B” ring, and double bonds were replaced by imine bonds and isometric heterocycles such as naphthyl and imidazole, or synthetic resveratrol oligomers. The structures, synthetic routes, and evaluation of the biological activities of these compounds are discussed. These are aimed at providing some references for the study of resveratrol derivatives in anti-breast cancer treatment.     

Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with synergistic antitumor efficiency

Ceramide (CE), a bioactive lipid with tumor suppression, has been widely used as a drug carrier and enhancer for cancer therapy. CE-based combination therapy was prone to be attractive in cancer therapy. In our previous study, the combination of CE and docetaxel (DTX) was proved to be an effective strategy for cancer therapy. To further improve the antitumor efficiency of DTX, the CE lipid-based nanosuspensions (LNS) was prepared for the delivery of DTX to exhibit synergistic therapeutic effect. The enhanced delivery and synergistic therapeutic effect of DTX-loaded CE-LNS (CE?+?DTX-LNS) were evaluated. CE?+?DTX-LNS exhibited spherical or ellipsoidal shape, uniform particle size distribution (108.1?±?3.8?nm), sustained release characteristics and good stability in vitro. Notably, CE?+?DTX-LNS could effectively co-localize CE and DTX into same tumor cell and subsequently play synergistic cell damage effect compared with CE-LNS?+?DTX-LNS (p?in vivo fluorescence imaging results showed that CE?+?DTX-LNS could effectively prolong the in vivo circulation time and enhance the accumulation in tumor sites. Moreover, the antitumor efficacy of CE?+?DTX-LNS observed in B16 murine melanoma model was 93.94?±?2.77%, significantly higher than that of CE-LNS, DTX-LNS, Duopafei® (p?p?相似文献   

国产多西他赛联合顺铂治疗复发乳癌多中心Ⅱ期临床试验

目的:评价国产多西他赛治疗蕙环类药治疗后复发乳癌的疗效及安全性。方法:采用多中心随机阳性药物对照方法,213例复发乳癌患者随机分为试验组105例和对照组108例。试验组d1给予注射用多西他赛60～70 mg·m～(-2),加5%葡萄糖溶液250mL静脉滴注;d3～d5给予顺铂25～30 mg·m～(-2),加生理氯化钠溶液500 mL静脉滴注。21～28d为1个周期,共2～3个周期。对照组:以已上市的国产注射用多西他赛作为阳性对照药取代试验用药进入上述方案。治疗2个周期后评价疗效及不良反应。结果:入组213例患者,200例完成试验,13例脱落。试验组99例,对照组101例。有效率(CR+PR)试验组42．42%(42/99),对照组37．62%(38/101),两组差异无显著性(P＞0．05)。主要Ⅲ～Ⅳ度不良反应为白细胞降低(试验组和对照组分别为20．95%和12．15%,P＞0．05)、恶心呕吐(分别为12．38%和7．48%,P＞0．05)、中性粒细胞降低(分别为11．43%和5．61%,P＞0．05)、腹泻(分别为7．62%和1．87%,P＞0．05)、脱发(分别为1．90%和0%,P＞0．05)、口腔溃疡(分别为1．90%和0%, P＞0．05)和血小板下降(分别为0．95%和0%,P＞0．05)。结论:多西他赛联合顺铂治疗复发乳腺癌疗效确切、且与已上市的国产多西他赛联合顺铂方案疗效相近,不良反应可耐受,有临床应用价值。     

铜绿假单胞茵注射液对人乳腺癌细胞的体外杀伤及促凋亡作用研究

目的研究铜绿假单胞菌（pseudo—monas aeruginosa,PA-MSHA）注射液在体外实验中对人乳腺癌细胞（MCF-7）凋亡和增殖的影响,并探讨其可能的作用机制。方法应用MTT比色法检测铜绿假单胞菌注射液对体外培养的MCF-7细胞增殖抑制作用,应用流式细胞术检测铜绿假单胞菌注射液诱导乳腺癌细胞凋亡,检测其对细胞周期的影响。用Hoechst33258染色法染色,荧光显微镜检测铜绿假单胞菌注射液诱导体外培养的MCF-7肿瘤细胞凋亡的形态学改变。结果铜绿假单胞菌注射液抑制MCK7细胞增殖,呈剂量和时间依赖性;与对照组相比,铜绿假单胞菌注射液组MCF7细胞的凋亡率明显增高（P〈0．01）、G0／G1期细胞比例明显增高、S期细胞所占百分比明显降低（P〈0．05）,染色荧光显微镜检测发现PAMSHA能诱导体外培养的肿瘤细胞呈现明显的凋亡图像。结论铜绿假单胞菌注射液可能通过对细胞周期中G0／G1期阻滞,诱导MCF-7细胞凋亡,从而抑制MCF-7细胞的增殖。     

低分子季铵化壳聚糖对乳腺癌细胞作用的研究

目的研究低分子季铵化壳聚糖对MCF-7乳腺癌细胞的作用,探讨其抑制肿瘤的作用机理。方法应用四甲基偶氮唑蓝(MTT)法、流式细胞仪检测低分子季铵化壳聚糖对MCF-7乳腺癌细胞生长的影响,采用端粒酶试剂盒考察其对端粒酶的影响。结果低分子季铵化壳聚糖可抑制MCF-7乳腺癌细胞的生长,作用于细胞周期G1期,抑制端粒酶活性。结论低分子季铵化壳聚糖能够诱导MCF-7乳腺癌细胞的凋亡,具有一定的抑瘤作用。     

乳腺癌MCF-7细胞系中侧群细胞分选及其生物学特性

目的 分离乳腺癌MCF-7细胞系中的侧群细胞(SP)并观察其生物学特性.方法 利用流式细胞荧光分选法将乳腺癌MCF-7细胞系分成SP和非SP细胞两个亚群.对两个亚群细胞采用软琼脂克隆形成实验观察其增殖能力.结果 MCF-7细胞株中分选出SP细胞占(6.5±0.4)％;SP细胞的体外克隆形成率为(38.5±9.4)％,高于非SP细胞的(8.4±2,6)％(t=5.34,P＜0.05).结论 乳腺癌MCF-7细胞中的SP细胞富集了乳腺癌于细胞,其增殖能力强于非SP细胞,表明SP表型的肿瘤细胞在乳腺癌的生长中具有重要的地位.     

尿石素A对乳腺癌细胞MCF-7增殖、凋亡的影响及其机制研究

目的 研究尿石素A对乳腺癌细胞MCF-7增殖、凋亡的影响并探讨其作用机制。方法 CCK-8法考察不同浓度尿石素A作用12、24、36、48 h对MCF-7细胞增殖能力的影响;细胞凋亡染色法考察20、40 μmol/L的尿石素A对MCF-7细胞凋亡的影响;实时荧光定量PCR（RT-qPCR）检测c-Myc、Cyclin D1、Bcl-2、Bax mRNA的表达水平;Western blotting法检测c-Myc、Cyclin D1、Bcl-2、Bax蛋白的表达水平。结果 尿石素A对MCF-7细胞增殖具有抑制作用且呈时间浓度相关性;细胞凋亡染色显示,20、40 μmol/L尿石素A给药后均能够诱导MCF-7细胞凋亡;RT-qPCR及Western blotting结果显示,20、40 μmol/L尿石素A能够显著降低MCF-7细胞中c-Myc、Cyclin D1、Bcl-2 mRNA及蛋白的表达水平（P<0.05、0.01）,升高Bax mRNA及蛋白的表达水平（P<0.05、0.01）。结论 尿石素A具有抑制MCF-7细胞增殖并诱导其凋亡的作用,其作用机制可能与抑制c-Myc、Cyclin D1、Bcl-2表达,升高Bax表达水平有关。     

Design,synthesis and antibreast cancer MCF-7 cells biological evaluation of heterocyclic analogs of resveratrol

A new series of resveratrol heterocyclic analogs (4a–m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure–activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC₅₀ = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC₅₀ = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4′-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F₁-ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.     

LncRNA ENST00000448869.1与Nestin互作拮抗西达苯胺对乳腺癌MCF-7细胞的作用

近年来,组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACi)作为低毒、有效的抗肿瘤药物越来越受到人们的关注,西达苯胺(chidamide)是第三代口服型、针对组蛋白去乙酰化酶(histone deacetylase,HDAC)1、2、3和10亚型的苯胺类的HDACi[1]。西达苯胺通过表观遗传修饰影响乳腺癌细胞的生长[2]。长链非编码RNA(long non-coding RNA,LncRNA)属于一类含有200多个核苷酸的非编码转录物,可以通过与DNA、RNA或蛋白质相互作用,在表观遗传学、转录及转录后水平调控基因的表达,参与多种病理生理过程[3-4]。     

丹蒽醌对乳腺癌细胞MCF-7增殖及侵袭转移的抑制作用及其作用机制研究

目的 研究丹蒽醌对乳腺癌细胞MCF-7增殖及侵袭转移的抑制作用,并探讨其作用机制。方法 CCK-8法检测不同浓度（10、20、40、60、80、100 μmol/L）的丹蒽醌作用24、48 h对乳腺癌细胞MCF-7增殖能力的影响;Transwell实验考察丹蒽醌对乳腺癌细胞MCF-7侵袭转移能力的影响。实时荧光当量PCR（RT-qPCR）法检测c-Myc、Cyclin D1 mRNA的表达水平;Western blotting法检测p-AMPKα、ACC、c-Myc、Cyclin D1蛋白的表达水平。结果 不同浓度的丹蒽醌作用不同时间对乳腺癌细胞MCF-7增殖均具有抑制作用;20、40 μmol/L的丹蒽醌能够明显的抑制乳腺癌细胞MCF-7的侵袭转移,同时能够激活p-AMPKα的表达,抑制ACC、c-Myc、Cyclin D1等基因的表达,从而抑制乳腺癌细胞MCF-7增殖。结论 丹蒽醌对乳腺癌细胞MCF-7增殖及侵袭转移具有抑制作用,其作用机制可能与激活AMPK信号通路抑制c-Myc、Cyclin D1等增殖相关基因表达有关。     

Novel plant-derived target drugs: a step forward from licorice?

Isoliquiritigenin (ISL) is a chalcone compound with valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer and anti-allergic activities. With regard to anticancer property, ISL was able to suppress HIF-1α level, VEGF expression and secretion, cell migration and to decrease the expression and secretion of MMP-9/-2. These effects may be mediated through inhibition of p38, PI3K/Akt and NF-κB signaling pathways. Thus, low concentration of ISL may have therapeutic potential in the treatment of aggressive breast carcinoma and other neoplasms.     

Curcumin: a calixarene derivative micelle potentiates anti-breast cancer stem cells effects in xenografted,triple-negative breast cancer mouse models

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease with no approved targeted therapy. Curcumin has shown therapeutic potential against TNBC, but it shows low bioavailability and low efficacy when administered as a free drug. Here we describe a novel vehicle for in vivo delivery of curcumin based on the phosphorylated calixarene POCA4C6. Curcumin-loaded POCA4C6 micelles (CPM) were prepared using the thin-film method and they showed a unilamellar structure with an average particle size of 3.86?nm. The micelles showed high curcumin encapsulation efficiency and loading was based on liquid chromatography-tandem mass spectrometry. Studies with cell cultures suggest that CPM can sustainably release curcumin in a pH-dependent manner. The micelles efficiently inhibited proliferation, invasion, migration and tumor spheroid formation by BT-549 human breast cancer cells. These effects involved increased apoptosis and reduced levels of nuclear β-catenin and androgen receptor. After injection into tumor xenografts, CPM persisted in the tumor tissue and efficiently inhibited tumor growth without causing obvious systemic toxicity. CPM also significantly reduced levels of CD44⁺/CD133⁺ breast cancer stem cells. Our results highlight the potential of CPM as an effective therapy against TNBC.     

多烯紫杉醇联合顺铂治疗晚期乳腺癌疗效观察

目的:观察国产多烯紫杉醇(艾素)联合顺铂治疗晚期乳腺癌的疗效及毒副反应。方法:21例患者均有病理学诊断及可评价的客观指标。采用多烯紫杉醇35mg/m2,静脉滴注1h,第1天、第8天及第15天,顺铂(DDP)为30mg/m2静脉滴注,第2天、第3天及第4天,28d为1个周期,所有患者均至少接受2个周期的化疗。结果:完全缓解(CR)1例,部分缓解(PR)11例,总有效率57.14%。主要毒副反应为骨髓抑制和脱发。结论:多烯紫杉醇联合顺铂治疗晚期乳腺癌有效率较高,毒副反应较小,值得临床进一步研究。     

人参皂苷Rg_3对失巢凋亡耐受乳腺癌细胞MCF-7抑制作用

目的研究人参皂苷Rg3对失巢凋亡耐受的乳腺癌细胞MCF-7生长抑制作用。方法应用多聚2-羟乙基甲基丙烯酸酯(poly-hema)覆盖的细胞培养板,筛选出具有失巢凋亡耐受的乳腺癌细胞MCF-7,考察失巢凋亡耐受癌细胞的生长速率和侵袭力,并利用流式细胞仪检测人参皂苷Rg3对失巢凋亡耐受癌细胞MCF-7的周期分布和细胞凋亡。结果与阿霉素对照组相比,人参皂苷Rg3能显著抑制失巢凋亡耐受的乳腺癌细胞MCF-7的生长(P<0.01),并导致失巢凋亡耐受细胞MCF-7的G0/G1期细胞比例显著增加(P<0.05)。结论人参皂苷Rg3有效抑制失巢凋亡耐受的乳腺癌细胞MCF-7生长,其作用机制可能与人参皂苷Rg3使失巢凋亡耐受乳腺癌细胞MCF-7细胞周期停滞有关。