廿二碳六烯酸脂质过氧化作用对阿霉素细胞毒活性的影响

目的：探讨廿二碳六烯酸（DHA）影响阿霉素（ADM）细胞毒活性的机理是否通过DHA的脂质过氧化作用。方法：在培养的人乳腺癌MDA－MB－435s细胞株中加入不同配伍的细胞毒药物,多不饱和脂肪酸（PUFAs),前氧化剂VitC和Vit K3混合物及抗氧化剂VitE等,在细胞的抽提物中以TBA法每24小时测定脂质过氧化产物丙二醛（MDA）及用亚硝酸盐分光光度法测定一氧化氮（NO）的含量,并作出MDA,NO含量与细胞毒性间的剂量一效应相关直线。结果：从细胞培养的第三天开始,出现明显的细胞活力变化,同时伴有脂质过氧化物MDA水平的增加及NO含量的降低,细胞抽提物中MDA及NO含量与细胞毒性之间存在直线相关关系。结论：DHA能明显增加ADM对MDA－MB－435s细胞株的细胞毒活性,机理之一是DHA增强了瘤细胞内的脂质过氧化作用。     

pcDNA3.1-asHpa对高转移性人乳腺癌细胞系侵袭力和黏附力的影响

目的探索pcDNA3.1asHpa对高转移性人乳腺癌细胞株MDA MB435S侵袭力和黏附力的作用。方法以质粒pcDNA3.1为载体,将乙酰肝素酶信号密码的DNA片段反向插入得到反义乙酰肝素酶信号密码真核表达载体(pcDNA3.1asHpa),以脂质体共转染人乳腺癌细胞MDA MB435S,以Boyden侵袭小室实验检测癌细胞侵袭力的变化,以细胞贴壁能力的变化检测其黏附力的变化。结果与正常对照组(侵袭率为54.3%,贴壁细胞数为22.91/视野)及空载体转染组(侵袭率为42.6%,贴壁细胞数为19.17/视野)相比,经pcDNA3.1asHpa转染的细胞侵袭力(16.3%)受到一定的抑制,黏附力(贴壁细胞数为21.36/视野)没有明显的变化。结论pcD NA3.1asHpa对人乳腺癌细胞株MDA MB435S的侵袭力有一定的抑制作用,对黏附力无显著影响。     

热激蛋白在乳腺癌细胞中的表达及其意义

目的：探讨热激蛋白（heat shock protein，HSP）90、70、27在高转移性乳腺癌细胞株MDA—MB-435s和MDA—MB-231中的表达情况及其意义。方法：MTT法检测HSP90抑制剂geldanamycin（GA）对2株乳腺癌细胞株粘附基质胶能力的影响；侵袭小室重组人工基底膜侵袭实验检测HSP90抑制剂GA对2株细胞的侵袭能力的影响；RT—PCR和Western blot实验检测2株细胞中HSP90、HSP70和HSP27mRNA及其蛋白质水平的表达差异。结果：GA能够明显抑制MDA—MB435s和MDA-MB-231细胞粘附基质胶的能力（P〈0．01）；2株高转移性乳腺癌细胞株的侵袭能力比较无显著性差异（P〉0．05），GA能够明显抑制2株乳腺癌细胞的侵袭能力，与对照组相比，MDA—MB-231细胞侵袭能力下降（P〈0．05），MDA-MB-435s细胞的侵袭能力下降更为明显（P〈0．01）。MDA—MB-435s细胞中HSP90蛋白质和HSP90αmRNA表达水平都明显高于MDA-MB-231细胞（P〈0．01），MDA-MB-435s和MDA—MB-231细胞中HSP90βmRNA表达水平没有显著差异（P〉0．05）；MDA-MB-231细胞中HSP27的mRNA和蛋白质的表达水平均明显高于MDA—MB-435s细胞（P〈0．01）；MDA-MB-435s细胞中HSP70蛋白质的表达水平与MDA-MB-231细胞没有显著性差异（P〉0．05），HSP70mRNA表达水平低于MDA—MB-231细胞（P〈0．05）。结论：HSP表达特性与乳腺癌细胞的粘附、侵袭能力相关；MDA—MB-435s细胞中HSP90较高水平表达，MDA-MB-231细胞中HSP27表达水平较高。     

EGCG对人乳腺癌MDA-MB-435细胞株细胞增殖的抑制及机制

目的：研究绿茶提取物表没食子儿茶素—3—没食子酸酯(epigalloeateehin—3 gallste，EGCG)对人乳腺癌细胞株细胞周期的影响及机制。方法：利用细胞增殖测定试剂盒(Cell Proliferation Assay kit)来制作细胞生长曲线；流式细胞仪分析EGCG作用于人乳腺癌MDA—MB—435细胞株前后细胞周期的变化；RT—PCR及Western印迹法研究肿瘤细胞株加药干预前后细胞周期抑制因子p21^waf1/cip1的mRNA及蛋白表达的变化。结果：EGCG可明显抑制乳腺癌细胞MDA—MB—435细胞的增殖活性，40μg／ml EGCG干预后，MDA-M-B435细胞主要阻滞于G0／G1期，在24小时阻滞最为明显。在48及72小时也有阻滞。对照组G0／G1期的比例49．92％，40μg／ml EGCG干预24、48及72小时后G0／G1期的比例分别为71．56％、67．20％和61．59％。EGCG 40μg／ml处理肿瘤细胞株细胞后24小时可检测p21 mRNA和蛋白表达提高。结论：绿茶有效成分可抑制乳腺癌细胞的增殖，这可能与其诱导p21表达从而抑制细胞周期的时相转换有关，这表明绿茶可能在乳腺癌的治疗上具有一定的前景。     

β2肾上腺素能受体在乳腺癌细胞中的表达及对侵袭能力的影响

目的：探讨β2肾上腺素能受体（β2 adrenergic receptor，β2-AR）在人乳腺癌细胞株中的表达以及对乳腺癌细胞侵袭能力的影响。方法：RT—PCR法检测10种乳腺癌细胞株及正常乳腺上皮细胞中β2-AR的表达；用脂质体转染法将卢2“尺基因转入乳腺癌细胞MDA—MB-435；用细胞侵袭实验（Transwell）检测亲本细胞及转染细胞的侵袭能力。结果：β2-AR在正常乳腺上皮细胞HBL-100及乳腺癌细胞BT-549、HCC1937、BCaP-37中表达；在乳腺癌细胞MDA—MB-435、MDA—MB-435HM、MCF-7、T47D中基本无表达；在乳腺癌细胞MDA—MB-231、MDA-MB-231HM、MDA—MB-468中高表达。细胞侵袭实验证实表达B2-AR蛋白的MDA—MB-231及稳定转染卢2-AR基因的细胞克隆MDA—MB-435β2-AR可由β2-AR受体激动剂去甲肾上腺素趋化而定向迁移及侵袭。结论：β2-AR在多种乳腺癌细胞株中表达；转染β2-AR可使乳腺癌细胞的侵袭能力增强。     

5-Aza-CdR和TSA联合调控乳腺癌maspin基因表达的研究

目的：研究5-氮-2＇-脱氧胞苷（5-Aza—CdR）和曲古菌素A（TSA）对乳腺癌MDA-MB-435S细胞增殖及抑癌基因maspin表达的影响。方法：用特异性甲基转移酶抑制剂5-Aza—CdR和组蛋白去乙酰酶抑制剂TSA分别单独和联合作用MDA—MB-435S乳腺癌细胞株5～8d，用MTT比色法观察细胞在药物作用前后的生长活性；RT—PCR检测细胞作用前后maspin mRNA的表达。结果：5μmol／L5-Aza-CdR作用乳腺癌细胞株MDA—MB-435S8d后，与对照组比较能明显抑制肿瘤细胞的生长；不同浓度TSA作用该细胞5d后，在〉100ng／mL浓度时才能显著的抑制该细胞的增殖。RT—PCR显示，5-Aza—CdR和TSA联合作用时可显著的诱导maspin mRNA的重新表达；而两药单用时其诱导作用相对较弱。结论：在人乳腺癌MDA—MB435S细胞中，maspin基因可能因表观遗传改变而导致转录失活，maspin基因的重新表达能有效的抑制细胞生长。5-Aza—CdR和TSA可作为乳腺癌治疗的新方向。     

抗ATPase F1α抗体MAb3D5AB1对荷A549肺腺癌小鼠的抑制作用

目的: 以乳腺癌细胞与成骨细胞共培养模拟乳腺癌骨转移微环境,观察在此微环境中降钙素基因相关肽( calcitonin generelated peptide,CGRP)对成骨细胞护骨素 （osteoprotegerin,OPG）及细胞核因子κB受体活化因子配体（receptor activator of nuclear factorkappa B ligand, RANKL;又称破骨细胞分化因子）表达的影响。方法：将转移性乳腺癌细胞MDAMB231或MDAMB435与成骨细胞MG63共培养,建立模拟乳腺癌骨转移微环境。行CGRP(1×108 mol/L)干预,应用RTPCR和Western Blotting技术检测干预后OPG和RANKL在mRNA和蛋白水平表达的变化。结果：MG63与MDAMB231或MDAMB435共培养环境中,RANKL mRNA及蛋白水平升高,而OPG mRNA和蛋白水平表达下降;CGRP处理后,共培养环境中RANKL mRNA及蛋白水平降低,OPG mRNA和蛋白水平升高 (均P<0.05)。结论：乳腺癌细胞能调节成骨细胞OPG/RANKL轴的表达,进而可能促进破骨细胞的活性,造成溶骨性破坏;CGRP 干预可逆转此调节作用,在乳腺癌骨转移的治疗中有潜在应用价值。     

放、热疗对荷瘤鼠肿瘤及肝MDA含量SOD活性的影响

目的探讨局部放热疗对S180荷瘤小鼠肿瘤及肝脏脂质过氧化水平及抗氧化能力的影响.方法本文采用硫代巴比妥酸(TBA)法及亚硝酸盐法,测定经局部放射、加温、放射合并加温后荷瘤小鼠肿瘤及肝脏丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性.各组数据采用SPSS软件包作两两比较分析.结果肿瘤组织MDA含量及SOD活性各组无差异(P＞0.05).肝组织加温组MDA含量高于放射组及实验对照组(P＜0.05),其它各组间MDA含量未见显著差异.加温组及放射合并加温组SOD活性均显著低于放射组及实验对照组(P＜0.01),其它各组间SOD活性未见显著差异.结论局部加温可能使荷瘤小鼠肝脏产生大量自由基,使SOD活性降低,MDA含量升高.因此,脂质过氧化损伤可能是加温对机体造成损伤的机制之一.     

多西紫杉醇对乳腺癌细胞增殖及侵袭力影响的研究

目的探索多西紫杉醇对人类乳腺非肿瘤细胞和乳腺癌细胞增殖及侵袭力的影响。方法应用MTT法检测多西紫杉醇对人乳腺细胞HBL100、人乳腺腺癌细胞MCF7和人乳腺导管癌细胞MDA MB435增殖的影响,采用Tran swell法明确该3株细胞的侵袭能力及多西紫杉醇对其侵袭能力的影响。结果在人乳腺细胞HBL100、人乳腺腺癌细胞MCF7和人乳腺导管癌细胞MDA MB435中,MDA MB435S侵袭力最高(425.20±54.09),MCF7次之(239.00±91.39),HBL100侵袭力最低(101.00±63.88)。1.0PPC(药物血浆峰浓度)的多西紫杉醇处理24h后,MDA MB435S和MCF7细胞的侵袭力分别为18.20±4.32和58.40±50.53,显著低于未处理的对照组(P值分别为0.000和0.013)。不同浓度的多西紫杉醇(0.1、1.0和10.0PPC)分别与3株细胞共同孵育24、48、72和96h,其对3株的增殖的抑制率均随着作用时间的延长以及给药浓度的增大而升高。结论多西紫杉醇对3株细胞的增殖抑制作用呈时间及浓度依赖性;并明显抑制MCF7和MDA MB435S细胞的侵袭能力。多西紫杉醇是一个通过抑制肿瘤细胞生长和侵袭双重途径起效的、具有很好的靶向性的抗肿瘤新药。     

甲基莲心碱对耐阿霉素人乳腺癌细胞多药耐药性的逆转

目的研究甲基莲心碱逆转耐阿霉素人乳腺癌细胞多药耐药性(MDR)的作用及机制。方法采用噻唑蓝(MTT)比色法检测细胞毒性;PI 染色流式细胞计数测定细胞凋亡;间接免疫荧光流式细胞术检测细胞 P-gp 的表达;HPLC 检测细胞内药物浓度。结果 Nef(1、5、10μmol·L~(-1))对人乳腺癌细胞(MCF-7/S)和耐阿霉素人乳腺癌细胞(MCF-7/ADM)无显著毒性作用。阿霉素(ADM)对敏感株 MCF-7/S 的 IC_(50)为0.13μg·mL~(-1)而对 MDR 细胞株 MCF-7/ADM 的 IC_(50)为11.63μg·mL~(-1),MCF-7/ADM 细胞较MCF-7/S 细胞对 ADM 耐药88倍,1、5、10μmol·L~(-1) Nef 能使 ADM 对 MCF-7/ADM 细胞的 IC_(50)从11.63μg·mL~(-1)依次下降至4.59、2.44、0.27μg·mL~(-1)。MCF-7/ADM 细胞对 ADM 具有凋亡抗性,Nef(1、5、10μmol·L~(-1))能克服 MCF-7/ADM 细胞对 ADM 的凋亡抗性。MCF-7/ADM 细胞较 MCF-7/S 细胞高表达 P-gp,Nef(10μmol·L~(-1))处理24h 后,MCF-7/ADM 细胞 P-gp 表达明显下降。ADM 作用3h 后,MCF-7/ADM 细胞内 ADM 的浓度比 MCF-7/S 细胞少2.8倍,Nef(10μmol·L~(-1))可使 MCF-7/ADM 细胞内 ADM 的浓度增加3.2倍,但并不增加 MCF-7/S 细胞内 ADM 的浓度。结论 Nef 具有逆转耐阿霉素人乳腺癌细胞 MDR 的作用,其作用机理与促进 MDR 细胞内 ADM 积累和下调 MDR 细胞 P-pg 表达有关。     

CXCL12 对人乳腺癌细胞株 MDA - MB - 435 失巢凋亡的研究

目的：研究趋化因子CXCL12对人乳腺癌高转移细胞系MDA—MB-435失巢凋亡的影响。方法：实验组培养基中加入终浓度为50ng／ml的CXCL12,对照组为无CXCLl2的DMEM培养基。两组细胞悬浮培养,建立人乳腺癌高转移细胞系MDA—MB-435失巢凋亡抵抗细胞模型。MTr检测CXCLl2对于失巢凋亡抵抗MDA—MB-435细胞系生长的影响,流式细胞仪检测两组细胞的凋亡情况,Transwe11实验检测细胞侵袭能力改变。结果：CXCLl2对于失巢凋亡抵抗MDA—MB-435细胞系在形态学方面与对照组相比无特异性改变。CXCLl2作用组失巢凋亡抵抗细胞增殖能力低于对照组,凋亡率增加,侵袭能力增加,穿过膜细胞数明显高于对照组（28±3．0VS15±2．4,P〈0．05）。结论：在人乳腺癌高转移细胞系MDA—MB-435失巢凋亡过程中,CXCL12能在一定程度上抑制失巢凋亡抵抗细胞的生长,但却能增加存活肿瘤细胞的侵袭性。     

五味子对乳腺癌细胞抑制作用的体外研究

目的:评估中药五味子抗癌有效成分木酚素及其代谢产物对雌激素受体阳性以及阴性的乳腺癌细胞株的体外作用,并评价五味子对于乳腺癌的体外杀伤作用。方法:利用ATP 生物荧光药物敏感性检测技术(ATP-TCA),检测五味子木酚素对50例乳腺癌的体外杀伤作用,并检测不同浓度五味子木酚素及其代谢物（END、ENL）对于ER（＋）的MCF-7、T47D和ER（－）的MDA-MB-231、MDA-MB-435细胞株的杀伤作用。评价五味子的体外作用有效率及其与雌激素受体表型是否相关。结果:五味子对乳腺癌患者的乳腺癌细胞具有明显的体外杀伤作用,体外有效率为34.0%(17/50);五味子木酚素以浓度依赖的方式,显著降低乳腺癌细胞株MCF-7、T47D、MDA-MB-435、MDA-MB-231的存活率,且该抑制作用和细胞雌激素受体的关系并不明显（P＞0.05）,五味子木酚素在较低浓度（0.1-30μmol/L）下对雌激素受体阳性乳腺癌细胞株MCF-7、T47D表现出促进增殖的作用,当浓度提高至100μmol/L后,五味子木酚素对MCF-7、T47D增殖表现出显著的抑制作用,并呈剂量-效应关系。木酚素的低浓度促进乳腺癌细胞增殖作用在雌激素受体阴性乳腺癌细胞株MDA-MB-435、MDA-MB-231中并不明显,当浓度提高至100μmol/L后,五味子木酚素对MDA-MB-435、MDA-MB-231增殖表现出显著的抑制作用,并呈剂量-效应关系。ENL、END(3-1000μmol/L)在体外对乳腺癌细胞株存在显著抑制作用（P＜0.05）,并有剂量依赖效应,未发现其与细胞雌激素受体表型有关联（P＞0.05）。木酚素在较低浓度区间（0.1-30μmol/L）促进ER(＋)细胞株的增殖,但对ER(－)细胞株作用不显著。结论:五味子对乳腺癌细胞系以及乳腺癌患者细胞均具有较强的杀伤作用,值得进一步临床研究和应用。     

Authentication of M14 melanoma cell line proves misidentification of MDA‐MB‐435 breast cancer cell line

A variety of analytical approaches have indicated that melanoma cell line UCLA‐SO‐M14 (M14) and breast carcinoma cell line MDA‐MB‐435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor and instead became falsely identified (through cross‐contamination or other means) as a cell line from a different donor. Initial studies concluded that MDA‐MB‐435 was the misidentified cell line and M14 was the authentic cell line, although contradictory evidence has been published, resulting in further confusion. To address this question, we obtained early samples of the melanoma cell line (M14), a lymphoblastoid cell line from the same donor (ML14), and donor serum preserved at the originator's institution. M14 samples were cryopreserved in December 1975, before MDA‐MB‐435 cells were established in culture. Through a series of molecular characterizations, including short tandem repeat (STR) profiling and cytogenetic analysis, we demonstrated that later samples of M14 and MDA‐MB‐435 correspond to samples of M14 frozen in 1975, to the lymphoblastoid cell line ML14, and to the melanoma donor's STR profile, sex and blood type. This work demonstrates conclusively that M14 is the authentic cell line and MDA‐MB‐435 is misidentified. With clear provenance information and authentication testing of early samples, it is possible to resolve debates regarding the origins of problematic cell lines that are widely used in cancer research.     

Enhancement of doxorubicin cytotoxicity by polyunsaturated fatty acids in the human breast tumor cell line MBA-MB-231: Relationship to lipid peroxidation

Exogenous polyunsaturated fatty acids modulate the cytotoxic activity of anti-cancer drugs. In this study, we examined whether lipid peroxidation is a potential mechanism through which fatty acids enhance drug cytotoxicity. We measured cell viability in the human breast cancer cell line MDA-MB-231 exposed to doxorubicin in the presence of non-cytotoxic concentrations of various polyunsaturated fatty acids for 6 days. To determine the role of lipid peroxidation, the hydroperoxide level was measured in cell extracts. Among all polyunsaturated fatty acids tested, docosahexaenoic acid (DHA, 22:6n-3) was the most potent in increasing doxorubicin cytotoxicity: cell viability decreased from 54% in the presence of 10⁻⁷ M doxorubicin alone to 21% when cells were incubated with doxorubicin and DHA. After addition of an oxidant system (sodium ascorbate/2-methyl-1,4-naphthoquinone) to cells incubated with doxorubicin and DHA, cell viability further decreased to 12%. Cell hydroperoxides increased commensurately. The effect of DHA on doxorubicin activity and lipid hydroperoxide formation was abolished by a lipid peroxidation inhibitor (dl-α-tocopherol) or when oleic acid (a non-peroxidizable fatty acid) was used in place of DHA. No effect was observed with mitoxantrone, a drug with a low peroxidation-generating potential. Thus, DHA may increase the efficacy of oxyradical-producing drugs through a mechanism involving a generation of lipoperoxides. This may lead in vivo to a modulation of tumor cell chemosensitivity by DHA and oxidant agents. Int. J. Cancer 75:578–583, 1998. © 1998 Wiley-Liss, Inc.     

Inhibiting autophagy increases epirubicin's cytotoxicity in breast cancer cells

Chemotherapy, radiotherapy, and endocrinotherapy are documented to induce autophagy among breast cancer cells, but the role of autophagy in this disease has been attributed as cytoprotective as well as tumor‐suppressing. Thus we studied MDA‐MB‐231 and SK‐BR‐3 breast cancer cell lines treated with epirubicin (EPI) to assess autophagy and apoptosis. We found out that EPI induced apoptosis and autophagy in both cell lines. The lysosomal inhibitor bafilomycin A1 inhibited cellular autophagy and enhanced EPI‐triggered apoptosis, perhaps due to inhibition of autolysosome formation, which then inhibited autophagic effects of engulfing and clearing damaged mitochondria. This inhibition increased mitochondrial cytochrome C release which augmented epirubicin‐induced caspase‐dependent apoptosis and cytotoxicity. In addition, the lysosomal neutralizing agent ammonia chloride (AC), and Atg7 knockdown by siRNA, could inhibit epirubicin‐triggered autophagy, enhance cytotoxicity, and increase caspase‐9‐ and caspase‐3‐dependent apoptosis. Thus, autophagy plays a prosurvival role in EPI‐treated MDA‐MB‐231 and SK‐BR‐3 cells, and autophagy inhibition can potentially reverse this effect and increase the cytotoxicity of EPI.     

整合素连接激酶在非小细胞肺癌中过度表达及促进肺癌细胞的侵袭和迁移

目的:探讨整合素连接激酶(ILK)在非小细胞肺癌(NSCLC)中的表达及在侵袭和迁移中的作用和相关分子机制。方法:免疫组化法检测ILK蛋白在NSCLC患者中的表达,细胞转染、siRNA干扰、细胞划痕试验、实时定量PCR、Westernblot方法探讨ILK在肺癌A549细胞中的表达及分子机制。结果:ILK蛋白在原发性NSCLC组织中过度表达30.6%(33/108)并且和TNM分期(P=0.001)、淋巴结转移(P=0.033)相关。ILK在A549细胞中过度表达并且通过下调E-cadherin,上调波形蛋白、纤维连接蛋白、Snail、Slug导致上皮-间质转化(EMT)。此外,NF-κB抑制剂BAY11-7028和小干扰靶RNA(siRNA)NF-p65可诱导E-cadher in的表达下调。结论:ILK在原发性NSCLC组织中高表达并与TNM分期和淋巴结转移相关,其促进肺癌细胞的侵袭和迁徙机制可能是经NF-κB信号通路诱导EMT所致。     

Persistent use of "false" cell lines

From HeLa and its multiple identities, to MDA‐MB‐435, erroneously and widely used as breast cancer cells, the history of cancer cell lines is rich in misidentification and cross‐contamination events. Despite the fact that these problems were regularly signaled during the last decades, many actors of research still seem to ignore them. A never‐ending story? Solutions exist, notably based on recent technical advances in cell line authentication (short tandem repeat analysis). However, a collaborative action involving users of cell lines, cell banks, journals and funding agencies is needed to achieve success. © 2007 Wiley‐Liss, Inc.     

Effects of dietary fatty acids on the proliferation, adhesion and metastatic potential of breast cancer cells: an experimental review

The dietary fat hypothesis postulates that dietary or exogenously derived fatty acids play an important role in the carcinogenesis, evolution and/or progression of breast cancer. In order to reveal possible underlying mechanisms of this hypothesis, we studied the influence of ω- 3 polyunsaturated fatty acids (PUFAs) -α-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA)-, ω-6 PUFAs-linoleic (LA), γ-linolenic (GLA) and arachidonic (ARA)- and monounsaturated ω- 9 oleic acid (OA) on the proliferation, adhesion and metastatic potential of human breast cancer cells in culture. GLA and the ω-3 PUFAs, ALA and DHA, inhibited significantly the cell growth of MCF-7 and MDA-MB-231 breast cancer cell lines, while EPA has less marked inhibitory effects. ω-6 PUFAs, LA and ARA, or ω- 9 OA had either no effect or caused a slight increase of proliferation. The attachment of breast cancer cells to the extracellular matrix components (type IV collagen, fibronectin and Matrigel) was significantly inhibited by ω-6 GLA and ω-3 PUFAs ALA, DHA and EPA. At concentrations which had no effect on cell growth over the duration of experiments the ω-6 PUFAs, LA and GLA, and the ω-3 PUFAs, ALA, DHA and EPA, had the ability to inhibit both cellular migration and invasion into type IV collagen and Matrigel. In summary, our findings indicate important differences in the ability of ω-3, ω-6 and ω-9 fatty acids to modulate prolif eration, attachment to extracellular matrix components, mo-tility and invasiveness of human breast carcinoma cells in vitro, with the GLA and all ω-3 PUFAs being the most effective inhibitors. Our data are consistent with the view that the type rather than the amount of dietary fatty acids is be more important in breast cancer development and progression.