PDF(Pubmed)
Abstract：
Dietary supplementation is proposed as a strategy to reduce the side effects of conventional chemotherapy for triple-negative breast cancer (TNBC). Chitosan oligosaccharides (COS), a functional carbohydrate, have been identified to potentially inhibit cancer cell proliferation. However, a detailed investigation is required to fully understand its exact influence, particularly in terms of COS composition. The antitumor activities of COS oligomers and its monomer of glucosamine, when combined with doxorubicin separately, were evaluated in MDA-MB-231 cells. Chitotriose was identified to have the most significant synergistic effect. Preincubation with chitotriose was observed to promote the entry of doxorubicin into the cell nuclei and induce morphological changes in the cells. Mechanism analysis at the transcriptional level revealed that the early growth response 1 (Egr1) gene was a key regulator in enhancing the suppressive effect. This gene was found to modulate the activity of its downstream gene, growth arrest, and DNA damage-inducible alpha (Gadd45a). The role of Egr1 was confirmed through a small interfering RNA test and function assay. These findings provide insight into the effect and underlying mechanism of chitotriose supplementation for TNBC therapy.
摘要：
膳食补充剂被建议作为减少三阴性乳腺癌（TNBC）常规化疗副作用的策略。壳寡糖(COS),功能性碳水化合物，已被确定可能抑制癌细胞增殖。然而,需要进行详细的调查以充分了解其确切影响，特别是在COS成分方面。COS低聚物及其葡糖胺单体的抗肿瘤活性,当分别与阿霉素联合使用时，在MDA-MB-231细胞中进行评价。三糖被鉴定为具有最显著的协同作用。观察到与几丁糖预孵育可促进阿霉素进入细胞核并诱导细胞的形态变化。转录水平的机制分析表明，早期生长反应1（Egr1）基因是增强抑制作用的关键调节因子。发现该基因调节其下游基因的活性，生长停滞,和DNA损伤诱导型α（Gadd45a）。通过小干扰RNA测试和功能测定证实了Egr1的作用。这些发现为TNBC治疗提供了对几丁三糖补充的作用和潜在机制的见解。
