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共轭亚油酸对肿瘤细胞MCF-7和MDA-MB-231的放射增敏作用

[Radiosensitizing effect of conjugated linoleic acid on tumor cells MCF-7 and MDA-MB-231].

作者信息

Drouin Geneviève, Douillette Annie, Lacasse Pierre, Paquette Benoit

机构信息

Départment de médicine mucléaire et radiobiologie, Faculté de médecine, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.

出版信息

Can J Physiol Pharmacol. 2004 Feb;82(2):94-102. doi: 10.1139/y04-003.

Abstract

Apoptotic pathways in breast cancer cells are frequently altered, reducing the efficiency of radiotherapy. Conjugated linoleic acid (CLA), known to trigger apoptosis, was tested as radiosensitizer in breast cancer cells MCF-7 and MDA-MB-231. The CLA-mix, made up of the isomers CLA-9cis 11trans and CLA-10trans 12cis, was compared to three purified isomers, i.e., the CLA-9cis 11cis, CLA-9cis 11trans, and CLA-10trans 12cis. Using the apoptotic marker YO-PRO-1, the CLA-9cis 11cis at 50 micro mol/L turned out to be the best apoptotic inducer leading to a 10-fold increase in MCF-7 cells and a 2,5-fold increase in MDA-MB-231 cells, comparatively to the CLA-mix. Contrary to previous studies on colorectal and prostate cancer cells, CLA-10trans 12cis does not lead to an apoptotic response on breast cancer cell lines MCF-7 and MDA-MB-231. Our results also suggest that the main components of the CLA-mix (CLA-9cis 11trans and CLA-10trans 12cis) are not involved in the induction of apoptosis in the breast cancer cells studied. A dose of 5 Gy did not induce apoptosis in MCF-7 and MDA-MB-231 cells. The addition of CLA-9cis 11cis or CLA-mix has allowed us to observe a radiation-induced apoptosis, with the CLA-9cis 11cis being about 8-fold better than the CLA-mix. CLA-9cis 11cis turned out to be the best radiosensitizer, although the isomers CLA-9cis 11trans and CLA-10trans 12cis have also reduced the cell survival following irradiation, but using a mechanism not related to apoptosis. In conclusion, the radiosensitizing property of CLA-9cis 11cis supports its potential as an agent to improve radiotherapy against breast carcinoma.

摘要

乳腺癌细胞中的凋亡途径常常发生改变,从而降低了放射治疗的效果。已知共轭亚油酸(CLA)可引发细胞凋亡,因此对其作为乳腺癌细胞MCF-7和MDA-MB-231的放射增敏剂进行了测试。将由CLA-9顺式11反式异构体和CLA-10反式12顺式异构体组成的CLA混合物与三种纯化的异构体,即CLA-9顺式11顺式、CLA-9顺式11反式和CLA-10反式12顺式进行比较。使用凋亡标记物YO-PRO-1,结果表明50微摩尔/升的CLA-9顺式11顺式是最佳的凋亡诱导剂,与CLA混合物相比,可使MCF-7细胞中的凋亡增加10倍,MDA-MB-231细胞中的凋亡增加2.5倍。与先前对结肠直肠癌和前列腺癌细胞的研究相反,CLA-10反式12顺式不会导致乳腺癌细胞系MCF-7和MDA-MB-231产生凋亡反应。我们的结果还表明,CLA混合物的主要成分(CLA-9顺式11反式和CLA-10反式12顺式)与所研究的乳腺癌细胞中的凋亡诱导无关。5 Gy的剂量未在MCF-7和MDA-MB-231细胞中诱导凋亡。添加CLA-9顺式11顺式或CLA混合物使我们能够观察到辐射诱导的凋亡,其中CLA-9顺式11顺式比CLA混合物好约8倍。CLA-9顺式11顺式被证明是最佳的放射增敏剂,尽管CLA-9顺式11反式和CLA-10反式12顺式异构体在照射后也降低了细胞存活率,但所使用的机制与凋亡无关。总之,CLA-9顺式11顺式的放射增敏特性支持了其作为改善乳腺癌放射治疗药物的潜力。

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