Abdolahi Mina, Shokri Fazel, Hosseini Mostafa, Shadanian Maryam, Saboor-Yaraghi Ali-Akbar
Department of Cellular and Molecular Nutrition, Faculty of Nutritional Sciences and Dietetics; Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
J Cancer Res Ther. 2016 Jan-Mar;12(1):204-8. doi: 10.4103/0973-1482.154071.
Breast cancer is one of the most women's cancers in the worldwide. In vivo and in vitro studies showed that all-trans-retinoic acid (ATRA) and docosahexaenoic acid (DHA) can modulate differentiation and apoptosis in both cancer and immune cells. Nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) activation in the presence of their ligands, plays a critical role in the proliferation, differentiation, and apoptosis of normal cells.
We hypothesized that ATRA and DHA, as ligands of RARs and RXRs respectively, may have synergistic effects on the induction of apoptosis in MCF-7 human mammary carcinoma cell lines.
MCF-7 cells were seeded in a 24-well plate at 3 × 105 cells per well. The cells were treated with 5 µM ATRA, 30 DHA, and various combinations of them over a 3-day trial. Apoptosis was measured by Annexin V-FITC kit and flow cytometery.
Our results showed that the combination treatment of ATRA and DHA (5 µM and 30 µM and half dose at 2.5 µM and 15 µM, respectively) in a dose-dependent manner induced apoptosis rate in MCF-7 cells significantly more than single treatment of ATRA or DHA, as compared to control group (P < 0.05).
We conclude that the combination of ATRA and DHA at the well-balanced proportion may be effective in cancer cell apoptosis. Further studies provide details about the potential synergistically effects of combination treatment of ATRA and DHA in growth inhibition and differentiation of human mammary cancer cells.
乳腺癌是全球范围内女性最常见的癌症之一。体内和体外研究表明，全反式维甲酸（ATRA）和二十二碳六烯酸（DHA）可调节癌细胞和免疫细胞的分化与凋亡。核维甲酸受体（RARs）和类视黄醇X受体（RXRs）在其配体存在下的激活，在正常细胞的增殖、分化和凋亡中起关键作用。
我们假设，分别作为RARs和RXRs配体的ATRA和DHA，可能对MCF-7人乳腺癌细胞系凋亡的诱导具有协同作用。
将MCF-7细胞以每孔3×10⁵个细胞接种于24孔板。在为期3天的试验中，用5μM ATRA、30μM DHA及其各种组合处理细胞。通过Annexin V-FITC试剂盒和流式细胞术检测凋亡情况。
我们的结果显示，与对照组相比，ATRA和DHA联合处理（分别为5μM和30μM以及半剂量2.5μM和15μM）以剂量依赖方式显著诱导MCF-7细胞凋亡率，比单独使用ATRA或DHA处理更高（P<0.05）。
我们得出结论，以平衡比例组合的ATRA和DHA可能对癌细胞凋亡有效。进一步的研究提供了关于ATRA和DHA联合处理在人乳腺癌细胞生长抑制和分化方面潜在协同作用的详细信息。
