School of Pharmacy and Medical Sciences, and UniSA Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia.
Clinical Nutrition Research Centre, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia.
Int J Mol Sci. 2018 Feb 6;19(2):484. doi: 10.3390/ijms19020484.
Although bone marrow and bone toxicities have been reported in breast cancer survivors, preventative strategies are yet to be developed. Clinical studies suggest consumption of long chain omega-3 polyunsaturated fatty acids (LCn3PUFA) can attenuate age-related bone loss, and recent animal studies also revealed benefits of LCn3PUFA in alleviating bone marrow and bone toxicities associated with methotrexate chemotherapy. Using a female rat model for one of the most commonly used anthracycline-containing breast cancer chemotherapy regimens (adriamycin + cyclophosphamide) (AC) chemotherapy, this study investigated potential effects of daily LCn3PUFA consumption in preserving bone marrow and bone microenvironment during chemotherapy. AC treatment for four cycles significantly reduced bone marrow cellularity and increased marrow adipocyte contents. It increased trabecular bone separation but no obvious changes in bone volume or bone cell densities. LCn3PUFA supplementation (375 mg/100 g/day) attenuated AC-induced bone marrow cell depletion and marrow adiposity. It also partially attenuated AC-induced increases in trabecular bone separation and the cell sizes and nuclear numbers of osteoclasts formed ex vivo from bone marrow cells isolated from AC-treated rats. This study suggests that LCn3PUFA supplementation may have beneficial effects in preventing bone marrow damage and partially protecting the bone during AC cancer chemotherapy.
虽然乳腺癌幸存者有骨髓和骨骼毒性的报道,但预防策略尚未开发。临床研究表明,长链 ω-3 多不饱和脂肪酸(LCn3PUFA)的摄入可以减轻与年龄相关的骨质流失,最近的动物研究也表明 LCn3PUFA 对减轻与甲氨蝶呤化疗相关的骨髓和骨骼毒性有一定益处。本研究使用雌性大鼠模型模拟最常用的蒽环类药物联合化疗方案(阿霉素+环磷酰胺)(AC)化疗,研究了在化疗期间每天摄入 LCn3PUFA 对维持骨髓和骨骼微环境的潜在影响。AC 治疗四个周期显著降低了骨髓细胞密度,增加了骨髓脂肪细胞含量。它增加了小梁骨分离,但骨体积或骨细胞密度没有明显变化。LCn3PUFA 补充(375mg/100g/天)减轻了 AC 引起的骨髓细胞耗竭和骨髓脂肪堆积。它还部分减轻了 AC 诱导的从 AC 处理的大鼠骨髓细胞分离的体外培养的破骨细胞的小梁骨分离以及细胞大小和核数目的增加。这项研究表明,LCn3PUFA 补充可能对预防骨髓损伤和部分保护 AC 癌症化疗期间的骨骼有有益作用。