Moxibustion regulates KDM4D expression and modulates lipid metabolism to inhibit tumor proliferation in CAC mice.

IF 6 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-05-05 DOI:10.1186/s12935-025-03798-8

Guona Li, Jindan Ma, Luyi Wu, Hanxiao Zhang, Yaying Lin, Hongxiao Xu, Muen Gu, Kunshan Li, Hongsheng Dong, Yan Huang, Huangan Wu

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引用次数: 0

Abstract

Background: Lysine demethylase 4D (KDM4D) and aberrant lipid metabolism are implicated in the development and progression of colitis-associated cancer (CAC). Moxibustion, a therapeutic approach in traditional Chinese medicine, can inhibit intestinal inflammation and improve the intestinal mucosa.

Methods: Mice were intraperitoneally injected with AOM, and three cycles of 3-2-2% DSS-free drinking water were administered to establish a CAC mouse model. Moxibustion and KDM4D inhibitor 5-c-8HQ intervention were performed for 30 days after modeling was completed. IHC staining was used to observe the expression of the nuclear-associated antigen Ki67 (Ki67), proliferating cell nuclear antigen (PCNA), and IL-33 in the colon. The expression of colon KDM4D and β-Catenin was observed by immunofluorescence staining and RT‒qPCR. LC‒MS pseudotargeted metabolomic sequencing was used to semiquantitatively detect the expression levels of lipids.

Results: Moxibustion inhibited the proliferation of colon tumors in CAC mice, improved histopathology, and reduced the expression of PCNA and Ki67 in the colon. Using kdm4d knockout technology, it was initially confirmed that kdm4d is a key gene affecting CAC tumor proliferation. The inhibition of colon tumor proliferation in CAC mice by moxibustion is associated with the suppression of abnormal activation of the colon KDM4D/β-Catenin signaling pathway. LC-MS-targeted metabolomics revealed abnormal lipid metabolism in the colons of CAC mice. Moxibustion may affect the cholinergic metabolism pathway in the colon of CAC mice and regulate lipids such as sphingomyelin SM (d18:1/26:0) and triacylglycerol TAG58:7 (18:0). After kdm4d knockout, lipid disorders in the colons of CAC mice were partially restored. The kdm4d gene may be involved in the mechanism underlying the effect of moxibustion on lipid metabolism in the CAC colon.

Conclusions: Moxibustion inhibited the proliferation of colon tumors in CAC mice, inhibited the activation of the tumor-promoting signaling pathway KDM4D/β-Catenin, and improved lipid metabolism disorders in the colon, thus providing a promising strategy for the clinical adjuvant treatment of colorectal cancer.

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艾灸通过调节KDM4D表达和脂质代谢抑制CAC小鼠肿瘤增殖。

背景：赖氨酸去甲基化酶4D （KDM4D）和异常脂质代谢与结肠炎相关癌症（CAC）的发生和进展有关。艾灸是中医的一种治疗方法，可以抑制肠道炎症，改善肠道黏膜。方法：小鼠腹腔注射AOM，并给予3次3-2-2%不含dss的饮用水，建立CAC小鼠模型。造模完成后进行艾灸和KDM4D抑制剂5-c-8HQ干预30 d。采用免疫组化染色法观察结肠组织中核相关抗原Ki67 （Ki67）、增殖细胞核抗原PCNA（增殖细胞核抗原）和IL-33的表达。免疫荧光染色和RT-qPCR观察结肠KDM4D和β-Catenin的表达。采用LC-MS伪靶向代谢组学测序半定量检测脂质表达水平。结果：艾灸能抑制CAC小鼠结肠肿瘤的增殖，改善组织病理学，降低结肠PCNA和Ki67的表达。利用kdm4d敲除技术，初步证实kdm4d是影响CAC肿瘤增殖的关键基因。艾灸对CAC小鼠结肠肿瘤增殖的抑制作用与抑制结肠KDM4D/β-Catenin信号通路异常激活有关。lc - ms靶向代谢组学显示CAC小鼠结肠脂质代谢异常。艾灸可影响CAC小鼠结肠胆碱能代谢途径，调节鞘磷脂SM （d18:1/26:0）、甘油三酯TAG58:7（18:0）等脂质。敲除kdm4d后，CAC小鼠结肠脂质紊乱得到部分恢复。kdm4d基因可能参与艾灸对CAC结肠脂质代谢影响的机制。结论：艾灸可抑制CAC小鼠结肠肿瘤的增殖，抑制促瘤信号通路KDM4D/β-Catenin的激活，改善结肠脂质代谢紊乱，为临床辅助治疗结直肠癌提供了一种有希望的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.