Evidence map›Paper›PMID 41257608›Full record

ArticleBMC gastroenterology2025

Nitidine chloride inhibits colorectal cancer by targeting BUB1: mechanistic insights from molecular dynamics simulation, spatial transcriptomics, and single-cell RNA sequencing.

Ke-Jun Wu, Jin-Cheng Li, Li-Min Liu, Xiao-Jue Huang, Liu-Hui Mo, Jing-Wen Ling, Kun-Hua Xiong, Wei Zhang, Rong-Quan He, Hui Li and 1 more

Abstract read
In one paragraph

Article in BMC gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Ke-Jun Wu *Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
Jin-Cheng Li *Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, 6 Shuang yong RD, Nanning, 530021, China.
Li-Min LiuDepartment of Toxicology, College of Pharmacy, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
Xiao-Jue HuangDepartment of Toxicology, College of Pharmacy, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
Liu-Hui MoDepartment of Toxicology, College of Pharmacy, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
Jing-Wen LingDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
Kun-Hua XiongDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
Wei ZhangDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
Rong-Quan HeDepartment of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China.
Hui LiDepartment of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China. lihui_gxmu@163.com.
Gang ChenDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, China. chengang@gxmu.edu.cn.

Funding

Guangxi Higher Education Undergraduate Teaching Reform Project 2024JGB148Guangxi Medical University "Four New" Project SX202403Guangxi Medical University Special Project on Educational and Teaching Reform for Clinical Disciplines 2025LCJG02Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project Z-A20250435Innovation Project of Guangxi Graduate Education JGY2023068
6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) is a prevalent malignancy with the efficacy of current treatments limited. Nitidine chloride (NC), a natural alkaloid, exhibits antitumor potential, but its mechanism in CRC remains unclear.

objectiveTo investigate the antitumor effects and mechanisms of NC in CRC for clinical therapeutic strategies.

methodsA Cell Counting Kit-8 was used to assess the viability of HCT116 cells. Xenograft mice received NC (2, 4, 8 mg/kg, intraperitoneal, once every other day for 2 weeks). Transmission electron microscopy and hematoxylin-eosin staining analyzed tumor ultrastructure and pathology. RNA sequencing, real-time quantitative polymerase chain reaction, and molecular dynamics simulation (MDS) examined gene expression and NC-budding uninhibited by benzimidazoles 1 (NC-BUB1) interaction. Single-cell RNA sequencing, spatial transcriptomics, immunohistochemistry, and chromatin immunoprecipitation sequencing explored BUB1 expression and RAD21 regulation. Immune correlation analysis was conducted using TISIDB, TIMER2.0, and deconvolution algorithms (CIBERSORT, CIBERSORT-ABS, EPIC, ESTIMATE, MCPcounter, quanTIseq, TIMER, xCell) to evaluate associations between BUB1 and immune factors or infiltration.

resultsNC inhibited HCT116 cells with time- and concentration-dependent half-maximal inhibitory concentration reduction. NC-treated tumors displayed apoptosis and reduced angiogenesis. Transcriptomics identified BUB1 as a core downregulated gene. Multi-omics confirmed BUB1 overexpression in CRC (1293 vs. 2299 samples; standardized mean difference = 1.77, area under the curve = 0.94) in proliferative/malignant regions. Immune analyses revealed that high BUB1 expression correlated negatively with antigen presentation molecules, chemokines/receptors, and immune cell infiltration (B cells, M2 macrophages, cancer-associated fibroblasts, endothelial cells), suggesting immune microenvironment suppression. BUB1 knockout inhibited CRC cells; NC reduced BUB1 expression. MDS showed a stable NC-BUB1 complex (- 8.8 kcal/mol). The RAD21-BUB1 axis exerted key regulatory roles.

conclusionNC exerts anti-CRC effects by downregulating BUB1, disrupting the RAD21-BUB1 axis, and alleviating BUB1-mediated immune suppression.

Indexed as

Antineoplastic AgentsBenzophenanthridinesCell Cycle ProteinsColorectal NeoplasmsProtein Serine-Threonine KinasesAnimalsApoptosisGene Expression Regulation, NeoplasticHCT116 CellsHumansMiceMolecular Dynamics SimulationSequence Analysis, RNASingle-Cell AnalysisTranscriptomeXenograft Model Antitumor AssaysAntineoplastic AgentsBenzophenanthridinesCell Cycle ProteinsnitidineProtein Serine-Threonine KinasesColorectal cancerImmune microenvironmentNitidine chlorideRAD21–BUB1 axisSingle-cell sequencingSpatial transcriptomics

Identifiers

PMID41257608
PMCPMC12628957

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.