Cai Fang, Sorg Olivier, Granci Virginie, Lecumberri Elena, Miralbell Raymond, Dupertuis Yves M, Pichard Claude
Clinical Nutrition, Geneva University Hospital, Geneva 1211, Switzerland.
Swiss Centre for Applied Human Toxicology, University of Geneva, Switzerland.
Clin Nutr. 2014 Feb;33(1):164-70. doi: 10.1016/j.clnu.2013.04.005. Epub 2013 Apr 23.
BACKGROUND & AIMS: This study aims at evaluating if docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) increases the efficacy of radiation therapy (RT) on two human colorectal cancer cell lines with different radio-sensitivity.
LS174T and HT-29 cells were treated with 20 or 50 μmol/L EPA or DHA followed by single X-ray RT of 0, 2 or 4 Gy, to evaluate cell survival, apoptosis, peroxide and malondialdehyde productions. Inflammation- and apoptosis-related proteins were analyzed by Western Blot. ANOVAs were used for statistical analysis.
LS174T was more sensitive to RT than HT-29. DHA and to a lesser extent EPA increased cell death, apoptosis and peroxide production after RT in LS174T and to a lesser extent in HT-29 (p < 0.05). This was associated with increased expression of heat shock protein 70, decreased expression of NF-kB p65, COX-2 and Bcl-2 proteins.
The effect of RT combination with DHA and to a lesser extent EPA was synergistic in the radio-sensitive LS174T cells, but additive in the radio-resistant HT-29 cells. This enhanced cytotoxicity was provoked at least partly by lipid peroxidation, which consequently modulated inflammatory response and induced apoptosis.
本研究旨在评估二十二碳六烯酸（DHA）或二十碳五烯酸（EPA）是否能提高放射治疗（RT）对两种具有不同放射敏感性的人结肠癌细胞系的疗效。
用20或50μmol/L的EPA或DHA处理LS174T和HT - 29细胞，然后进行0、2或4 Gy的单次X射线放射治疗，以评估细胞存活、凋亡、过氧化物和丙二醛的产生。通过蛋白质免疫印迹法分析炎症和凋亡相关蛋白。采用方差分析进行统计分析。
LS174T对放射治疗比HT - 29更敏感。DHA以及程度稍轻的EPA在放射治疗后增加了LS174T细胞的死亡、凋亡和过氧化物产生，在HT - 29细胞中增加程度稍轻（p < 0.05）。这与热休克蛋白70表达增加、NF - kB p65、COX - 2和Bcl - 2蛋白表达降低有关。
放射治疗联合DHA以及程度稍轻的EPA对放射敏感的LS174T细胞具有协同作用，但对放射抗性的HT - 29细胞具有相加作用。这种增强的细胞毒性至少部分是由脂质过氧化引起的，脂质过氧化进而调节炎症反应并诱导凋亡。
