[1]徐瞳,张荔,葛晓松,等.穿心莲内酯下调POLRMT抑制肺癌细胞天冬氨酸代谢实验研究[J].陕西中医,2025,46(10):1299-1304,1311.[doi:DOI:10.3969/j.issn.1000-7369.2025.10.001]
　XU Tong,ZHANG Li,GE Xiaosong,et al.Experimental study on andrographolide down-regulating POLRMT to inhibit aspartate metabolism in lung cancer cells[J].,2025,46(10):1299-1304,1311.[doi:DOI:10.3969/j.issn.1000-7369.2025.10.001]
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穿心莲内酯下调POLRMT抑制肺癌细胞天冬氨酸代谢实验研究

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年10期
页码:
1299-1304,1311
栏目:
基础研究
出版日期:
2025-10-05

文章信息/Info

Title:
Experimental study on andrographolide down-regulating POLRMT to inhibit aspartate metabolism in lung cancer cells
作者:
徐瞳1; 张荔2; 葛晓松1; 沈娣1
（1.江南大学附属医院，江苏 无锡 214000；2.上海中医药大学附属龙华医院，上海 200030）
Author(s):
XU Tong1; ZHANG Li2; GE Xiaosong1; SHEN Di1
(1.Affiliated Hospital of Jiangnan University,Wuxi 214000,China;2.Shanghai University of Traditional Chinese Medicine,Shanghai 200030,China)
关键词:
肺癌; 穿心莲内酯; 天冬氨酸; 线粒体RNA聚合酶; 代谢重编程; 增殖
Keywords:
Lung cancer; Andrographolide; Aspartate; Mitochondrial RNA polymerase; Metabolic reprogramming; Proliferation
分类号:
R 734.2
DOI:
DOI:10.3969/j.issn.1000-7369.2025.10.001
文献标志码:
A
摘要:
目的：研究中药单体穿心莲内酯（AD）抗肺癌的关键代谢靶点及作用机制。方法：通过ATPlite实验和细胞克隆形成实验检测AD对肺癌细胞增殖的影响。通过代谢组学检测和代谢通路富集分析等方法，解析AD对肺癌代谢物的影响，寻找关键代谢靶点。利用RNA-seq分析AD影响代谢的目的基因，并通过Western blot、RT-PCR实验进行验证。利用公共数据库分析目的基因在肺癌中的表达情况以及与肺癌患者总生存率的关系。结果：AD能够以时间和浓度依赖性的方式抑制A549、H1299肺癌细胞的增殖（P<0.01）。与对照组相比，AD处理肺癌细胞后显著改变了肿瘤细胞的代谢谱，下调了天冬氨酸、嘧啶代谢物（尿嘧啶核苷酸、尿嘧啶、尿苷）的水平（P<0.05）。RNA-seq、Western blot以及RT-PCR实验结果显示，AD处理组的天冬氨酸代谢相关基因POLRMT的mRNA表达量及蛋白表达量均低于对照组（P<0.01）。公共数据库分析结果显示在肺腺癌中，POLRMT的高表达与患者低生存率密切相关（P<0.05）。结论：AD能够有效抑制A549、H1299肺癌细胞的增殖，其抗癌作用可能与调控POLRMT-天冬氨酸代谢通路有关。
Abstract:
Objective:To investigate the key metabolic targets and mechanism of anti-lung cancer by andrographolide (AD).Methods:The effect of AD on the proliferation of lung cancer cells was detected by ATPlite assay and clony formation assay.Through metabolism detection and metabolic pathway enrichment analysis,the effects of AD on metabolites in lung cancer were analyzed,and the key metabolic targets were found.The target genes of AD affecting metabolism were analyzed by RNA-seq,and verified by Western blot and RT-PCR.Public databases were used to analyze the expression of target genes in lung cancer and its relationship with the overall survival rate of lung cancer patients.Results:AD inhibited the proliferation of A549 and H1299 lung cancer cells in a time and dose-dependent manner (P<0.01).Compared with the control group,AD significantly altered the metabolic profile of lung cancer cells,reducing the levels of aspartate and pyrimidine metabolites (urid ylic acid,uracil,uridine) (P<0.05).The results of RNA-seq,Western blot and RT-PCR experiments showed that the mRNA expression level and protein expression level of the aspartate metabolism-related gene POLRMT in the AD treatment group were both lower than those in the control group (P<0.01).The results of public database analysis showed that in lung adenocarcinoma,the high expression of POLRMT was closely related to the low survival rate of patients (P<0.05).Conclusion:AD can effectively inhibit the proliferation of A549 and H1299 lung cancer cells,and its anticancer effect may be related to the regulation of POLRMT-aspartate metabolism pathway.

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备注/Memo

备注/Memo:
国家自然科学基金青年基金资助项目（82405112）；江苏省卫生健康委员会指导性项目（Z2023020）
更新日期/Last Update: 2025-10-10