Yao Liang, Gu Chen, Ge Ruipeng, Zhang Xiaoqian, Meng Xinqian, Wang Lei, Peng Daiyin, Li Guozhuan
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
Anhui Academy of Chinese Medicine, Hefei, China.
Front Oncol. 2025 Mar 4;15:1529868. doi: 10.3389/fonc.2025.1529868. eCollection 2025.
Not all polysaccharides function as antitumor drugs, nor do they universally possess the same advantages regarding safety and biocompatibility. Those polysaccharides that are effective antitumor agents typically demonstrate superior safety profiles and biocompatibility compared to synthetic anticancer drugs, which can exhibit high toxicity and harmful side effects. polysaccharide (DHP) has been recognized for its potential bioactive properties, particularly in anti-tumor treatment. This study investigates the effects of DHP on the proliferation and apoptosis of HCT116 colon cancer cells.
DHP was extracted according to previously published experimental methods. The inhibitory effects of DHP were evaluated using IEC6, Caco-2, and HCT116 cell lines, with changes in cell morphology observed via transmission electron microscopy. After establishing the conditions for DHP administration, flow cytometry was employed to assess its effects on apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential of HCT116 cells. Additionally, immunoprecipitation, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and biomarker detection were utilized to investigate the mechanisms underlying DHP's inhibition of HCT116 cells and its impact on metabolic reprogramming.
In the present study, we observed that DHP treatment at 600 μg/ml for 24 h reduced HCT116 cell viability to 54.87%. In contrast, the inhibitory effect of DHP on the viability of IEC6 and Caco-2 cells was relatively mild. The specific mechanism involves DHP activating the mitochondrial apoptotic pathway leading to the downregulation of key metabolic intermediates and enzymes such as uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) and ST6Gal-I. By inhibiting ST6Gal-I activity, DHP activates the Fas/FasL signaling pathway. Additionally, DHP-induced ROS production effectively triggers apoptosis in HCT116 cells.
Our study demonstrates that DHP effectively inhibits the proliferation and induces apoptosis in HCT116 colon cancer cells through the activation of the Fas-FasL signaling pathway and metabolic reprogramming. The selective inhibitory effect of DHP on HCT116 cells, the activation of both death receptor and mitochondrial apoptotic pathways, and the modulation of metabolic reprogramming provide novel insights into the potential therapeutic strategies for colon cancer.
并非所有多糖都能作为抗肿瘤药物发挥作用，在安全性和生物相容性方面它们也并非普遍具有相同的优势。那些有效的抗肿瘤多糖通常显示出比合成抗癌药物更优越的安全性和生物相容性，合成抗癌药物可能具有高毒性和有害的副作用。多糖（DHP）因其潜在的生物活性特性而受到认可，尤其是在抗肿瘤治疗方面。本研究调查了DHP对HCT116结肠癌细胞增殖和凋亡的影响。
根据先前发表的实验方法提取DHP。使用IEC6、Caco-2和HCT116细胞系评估DHP的抑制作用，通过透射电子显微镜观察细胞形态的变化。在确定DHP给药条件后，采用流式细胞术评估其对HCT116细胞凋亡、活性氧（ROS）和线粒体膜电位的影响。此外，利用免疫沉淀、定量实时聚合酶链反应（qRT-PCR）、蛋白质印迹法和生物标志物检测来研究DHP抑制HCT116细胞的机制及其对代谢重编程的影响。
在本研究中，我们观察到600μg/ml的DHP处理24小时后，HCT116细胞活力降至54.87%。相比之下，DHP对IEC6和Caco-2细胞活力的抑制作用相对较弱。具体机制涉及DHP激活线粒体凋亡途径，导致关键代谢中间体和酶如尿苷二磷酸N-乙酰葡糖胺（UDP-GlcNAc）和ST6Gal-I的下调。通过抑制ST6Gal-I活性，DHP激活Fas/FasL信号通路。此外，DHP诱导的ROS产生有效地触发了HCT116细胞的凋亡。
我们的研究表明，DHP通过激活Fas-FasL信号通路和代谢重编程有效地抑制HCT116结肠癌细胞的增殖并诱导其凋亡。DHP对HCT116细胞的选择性抑制作用、死亡受体和线粒体凋亡途径的激活以及对代谢重编程的调节为结肠癌潜在治疗策略提供了新的见解。
