DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA.
DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA.
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DOI：
10.1007/s10549-013-2703-y
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发表时间：
2013-10
影响因子：
3.8
通讯作者：
Fernandes, Gabriel
中科院分区：
文献类型：
--
作者：
Rahman, Md Mizanur;Veigas, Jyothi Maria;Williams, Paul J.;Fernandes, Gabriel
乳腺癌患者经常发生骨转移，表现为溶骨性病变，导致剧烈疼痛和骨折。富含EPA和DHA的鱼油(FO)可以减轻乳腺癌的骨转移和相关的骨溶解作用，此前已有研究表明。然而，目前尚不清楚EPA和DHA是否对乳腺癌骨转移和相关的骨溶解有不同或相似的影响。经EPA和DHA处理的人乳腺癌细胞株的体外培养表明，DHA对乳腺癌细胞的增殖和侵袭的抑制作用比EPA更强。将双亲和荧光素酶基因编码的MDA-MB-231细胞注入裸鼠NCR nu/nu小鼠的心脏内，结果表明，DHA处理的小鼠骨中的乳腺癌细胞负荷显著低于EPA处理的小鼠，溶骨性病变也显著少于EPA处理的小鼠。通过荧光素酶强度测定的体内细胞迁移实验表明，DHA可抑制细胞向骨骼的迁移。此外，DHA治疗组骨组织中CD44和TRAP阳性区域的表达水平低于EPA治疗组。在胫骨内注射乳腺癌细胞的小鼠中也检测了乳腺癌细胞的负荷和溶骨性病变，发现DHA治疗的小鼠与EPA治疗的小鼠相比，乳腺癌细胞的生长和相关的骨溶解更少。最后，用耐阿霉素的人乳腺癌细胞株MCF-7dox检测DHA是否能提高MCF-7dox细胞对阿霉素的增敏作用。DHA可增强阿霉素对MCF-7dox细胞增殖和侵袭的抑制作用。有趣的是，耐药基因P-gp在DHA加阿霉素处理的细胞中也下调。总而言之，DHA比EPA更有效地减少乳腺癌的骨转移和相关的骨溶解，可能是通过抑制乳腺癌细胞向骨的迁移以及通过抑制破骨细胞性骨吸收。
Breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Attenuation of breast cancer metastasis to bone and associated osteolysis by fish oil (FO), rich in EPA and DHA, has been demonstrated previously. However, it was not known whether EPA and DHA differentially or similarly affect breast cancer bone metastasis and associated osteolysis. In vitro culture of parental and luciferase gene encoded MDA-MB-231 human breast cancer cell lines treated with EPA and DHA revealed that DHA inhibits proliferation and invasion of breast cancer cells more potently than EPA. Intra-cardiac injection of parental and luciferase gene encoded MDA-MB-231 cells to athymic NCr nu/nu mice demonstrated that DHA treated mice had significantly less breast cancer cell burden in bone, and also significantly less osteolytic lesions than EPA treated mice. In vivo cell migration assay as measured by luciferase intensity revealed that DHA attenuated cell migration specifically to the bone. Moreover, the DHA treated group showed reduced levels of CD44 and TRAP positive area in bone compared to EPA treated group. Breast cancer cell burden and osteolytic lesions were also examined in intra-tibially breast cancer cell injected mice and found less breast cancer cell growth and associated osteolysis in DHA treated mice as compared to EPA treated mice. Finally, doxorubicin resistant MCF-7 (MCF-7dox) human breast cancer cell line was used to examine if DHA can improve sensitization of MCF-7dox cells to doxorubicin. DHA improved the inhibitory effect of doxorubicin on proliferation and invasion of MCF-7dox cells. Interestingly, drug resistance gene P-gp was also down-regulated in DHA plus doxorubicin treated cells. In conclusion, DHA attenuates breast cancer bone metastasis and associated osteolysis more potently than EPA, possibly by inhibiting migration of breast cancer cell to the bone as well as by inhibiting osteoclastic bone resorption.
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发表时间：
2010-11-26
影响因子：
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作者：
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