Evidence map›Paper›PMID 41168435›Full record

ArticleNaunyn-Schmiedeberg's archives of pharmacology2026

5-Methoxyflavone inhibits the proliferation of lung adenocarcinoma cells through PI3K/AKT/GSK3β/β-catenin/Cyclin D1 signaling and attenuates chemoresistance and PD-L1 expression.

Yan Zhao, Yiwen Cui, Rong Li, Mingyong Li, Zhiwei He, Yingying Hu

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In one paragraph

Article in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

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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.

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Yan Zhao *Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
Yiwen Cui *Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
Rong LiDepartment of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
Mingyong LiDepartment of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.
Zhiwei HeDepartment of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. hezhiwei@gdmu.edu.cn.
Yingying HuDepartment of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. hyy@gdmu.edu.cn.

Funding

Medical Scientific Research Foundation of Guangdong Province A2021243National Natural Science Foundation of China 82102727PhD Start-up Foundation of Guangdong Medical University GDMUB2020020Science Foundation of traditional Chinese medicine administration of Guangdong Province 20221210
6 · The paper itself

Abstract

5-Methoxyflavone, a natural flavonoid compound, has been shown to exhibit pro-apoptotic effects in certain types of cancer. However, its function in lung adenocarcinoma (LUAD) is not known. This study is designed to investigate the anti-tumor effect of 5-methoxyflavone on LUAD. In vitro and in vivo experiments were performed to examine the impact of 5-methoxyflavone on the proliferation of LUAD cells. The target and biological activities of 5-methoxyflavone against LUAD were predicted by bioinformatics analysis. The effect of 5-methoxyflavone on cisplatin resistance was assessed by MTT and RT-qPCR. The programmed death-ligand 1 (PD-L1) expression was determined by western blot and immunofluorescence. 5-Methoxyflavone significantly inhibited the proliferation of LUAD cells by inducing G0/G1-phase arrest. Moreover, it suppressed tumor growth in a xenograft mouse model without causing organ toxicity. Mechanistic studies revealed that 5-methoxyflavone induced proteasomal degradation of cyclin D1 through inactivation of phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase-3β (PI3K/AKT/GSK3β) signaling. The addition of the AKT activator SC79 or the GSK3β inhibitor SB216763 reversed the reduction of cyclin D1 expression. Furthermore, 5-methoxyflavone might decrease the transcriptional level of cyclin D1 via downregulation of β-catenin expression (substrate of GSK3β). A combination of 5-methoxyflavone and cisplatin acted synergistically to overcome cisplatin resistance and reduced mRNA expression of resistant-associated genes in LUAD cells. Remarkably, 5-methoxyflavone hindered phosphorylation activation of STAT3, thus inhibiting PD-L1 expression in LUAD cells. In summary, we elucidated the anti-proliferative, chemo-sensitizing, and immunomodulatory effects of 5-methoxyflavone against LUAD, providing a potential new drug for the treatment of LUAD.

Indexed as

Adenocarcinoma of LungAntineoplastic AgentsB7-H1 AntigenFlavonesFlavonoidsLung NeoplasmsAnimalsbeta CateninCell Line, TumorCell ProliferationCisplatinCyclin D1Drug Resistance, NeoplasmGlycogen Synthase Kinase 3 betaHumansMiceAntineoplastic AgentsB7-H1 Antigenbeta CateninCCND1 protein, humanCD274 protein, humanCisplatinCTNNB1 protein, humanCyclin D1FlavonesFlavonoidsGlycogen Synthase Kinase 3 betaGSK3B protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-akt5-MethoxyflavoneChemoresistanceLung adenocarcinomaPD-L1PI3K/AKT/GSK3β/β-catenin/cyclin D1Proliferation

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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 OpenQuestion graph.