Davison Zoë, Nicholson Robert I, Hiscox Stephen, Heard Charles M
School of Pharmacy & Pharmaceutical Sciences, Cardiff University, CF10 3NB, Cardiff, United Kingdom.
Open Biochem J. 2018 Aug 31;12:130-148. doi: 10.2174/1874091X01812010130. eCollection 2018.
There is an urgent need for new therapies to treat cancer metastasis. Fish oil, with high omega 3 fatty acid content, has shown anticancer activity and signal transduction inhibitors have shown anti-metastatic properties.
To provide preliminary data on the anti-migration potential of signal transduction inhibitors and co-administered fish oil.
MCF-7, TamR and FasR breast cancer cell lines were used to determine the effects of combinations of PD98059, LY294002 and fish oil in growth assays. Modulations of p-Src and COX-2, both mediators of motility and invasion, were then determined by Western blotting and IHC to ascertain effects on migration potential.
Migration rates for the three cell lines examined were ranked: FasR>TamR>MCF-7 ( <0.05). Addition of fish oil reduced the number of TamR cells migrating after 48h ( <0.05), while the addition of PD98059 and LY294002 also decreased migratory potential of TamR cells ( <0.05). Addition of PD98059 and LY294002 to TamR cells did not result in a significant decrease in p-Src levels; as was the case when PD98059, LY294002 and 4-hydroxytamoxifen were added to MCF-7 cells. However, the co-administration of fish oil markedly reduced p-Src and COX-2 expression in both cell lines.
Co-administration of a commercial fish oil with signal transduction inhibitors results in decreased cell migration an unknown co-operative mechanism and could constitute a novel approach for the treatment of breast cancer metastasis.
迫切需要新的疗法来治疗癌症转移。富含ω-3脂肪酸的鱼油已显示出抗癌活性,信号转导抑制剂也已显示出抗转移特性。
提供关于信号转导抑制剂与联合使用的鱼油的抗迁移潜力的初步数据。
使用MCF-7、TamR和FasR乳腺癌细胞系来确定PD98059、LY294002和鱼油组合在生长试验中的作用。然后通过蛋白质免疫印迹法和免疫组化法测定运动和侵袭的两种介质p-Src和COX-2的调节情况,以确定对迁移潜力的影响。
所检测的三种细胞系的迁移率排序为:FasR>TamR>MCF-7(P<0.05)。添加鱼油可减少48小时后迁移的TamR细胞数量(P<0.05),而添加PD98059和LY294002也可降低TamR细胞的迁移潜力(P<0.05)。向TamR细胞中添加PD98059和LY294002不会导致p-Src水平显著降低;向MCF-7细胞中添加PD98059、LY294002和4-羟基他莫昔芬时也是如此。然而,鱼油的联合使用显著降低了两种细胞系中p-Src和COX-2的表达。
商业鱼油与信号转导抑制剂联合使用可导致细胞迁移减少,其协同机制未知,可能构成一种治疗乳腺癌转移的新方法。