Chitotriose Enhanced Antitumor Activity of Doxorubicin through Egr1 Upregulation in MDA-MB-231 Cells

文献类型： 外文期刊

第一作者： Li, Heng

作者： Li, Heng;Ji, Ke;Geng, Yan;Gong, Jinsong;Shi, Jinsong;Liu, Peng;Zhang, Chao;Ding, Zhenzhong;Xu, Zhenghong

作者机构：

关键词： chitotriose; triple-negative breast cancer (TNBC); antitumor activity; RNA sequencing; early growth response 1 (Egr1)

期刊名称：MARINE DRUGS （ 影响因子：5.4； 五年影响因子：5.5 ）

ISSN：

年卷期： 2024 年 22 卷 1 期

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收录情况： SCI

摘要： 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.

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