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Cited by 33Flavonoids in Medical ResearchCancer, Hypoxia, and MetabolismEsophageal Cancer Research and Treatment

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Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A

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Guo, Dongli, Jin, Jing, Liu, Jianghui, Wang, Yingying, Li, Daojuan, He, Yutong·2022·Drug Design, Development and Therapy
DOI 10.2147/dddt.s370114PMC PMC9346416
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Abstract

Purpose: To explore the mechanism of the effect of baicalein on radioresistance of esophageal cancer, and to provide ideas for the treatment of patients with poor radiotherapy effect of esophageal cancer. Methods: The glycolytic rate assay kit was used to detect the changes in glycolytic metabolism in esophageal cancer cells after treatment with baicalein, and mass spectrometry was used to detect whether baicalein could affect the level of glycolysis-related metabolites in esophageal cancer cells. The binding of baicalein to the target protein was simulated by molecular docking technique, the protein expression level was detected by Western Blot, and the changes in the cell cycle were detected by flow cytometry. Results: Radiation combined with baicalein could significantly inhibit the proliferation and migration of esophageal cancer cells compared with that of 6 Gy rays alone. The results of the glycolytic rate assay showed that baicalein could inhibit the glycolysis of esophageal cancer cells. Metabonomic studies showed that baicalein could affect the expression levels of glycolysis-related metabolites. The results of network pharmacology showed that baicalein could target several key glycolysis enzymes and glycolysis-related proteins, such as HIF-1A. The results of the WB experiment showed that glycolysis-related proteins and cycle-related proteins were down-regulated after baicalein treatment. Conclusion: The main mechanism of baicalein inhibiting radiation resistance of esophageal cancer cells is that targeting HIF-1A protein regulates glucose metabolism and then regulates Cyclin D1/CDK4 axis to change the cell cycle.

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Figure 1 Continue.
Figure 1 Continue.CC BY-NC · PubMed Central
Figure 1 Baicalein suppresses cell proliferation, migration, invasion and cell cycle in vitro. (A) Cell proliferation was detected by MTS assays after baicalein treated on KYSE150 cells. (B) Clonogenic assays were performed after baicalein treated on KYSE150 cells. (C) Migration was detected by Wound-Healing Assay after baicalein treated on KYSE 150 cells. (D) Invasion was detected by Transwell assays after baicalein treated on KYSE 150 cells. (E) The cell cycle of KYSE150 cells was assessed by flow cytometry. *p< 0.05.
Figure 1 Baicalein suppresses cell proliferation, migration, invasion and cell cycle in vitro. (A) Cell proliferation was detected by MTS assays after baicalein treated on KYSE150 cells. (B) Clonogenic assays were performed after baicalein treated on KYSE150 cells. (C) Migration was detected by Wound-Healing Assay after baicalein treated on KYSE 150 cells. (D) Invasion was detected by Transwell assays after baicalein treated on KYSE 150 cells. (E) The cell cycle of KYSE150 cells was assessed by flow cytometry. *p< 0.05.CC BY-NC · PubMed Central
Figure 2 Effect of baicalein combined with radiotherapy on esophageal cancer cells. (A and B) Baicalein combined with radiotherapy inhibits the proliferation of esophageal cancer cells. (C) Inhibitory effect of baicalein combined with radiotherapy on migration of esophageal cancer cells. *p< 0.05.
Figure 2 Effect of baicalein combined with radiotherapy on esophageal cancer cells. (A and B) Baicalein combined with radiotherapy inhibits the proliferation of esophageal cancer cells. (C) Inhibitory effect of baicalein combined with radiotherapy on migration of esophageal cancer cells. *p< 0.05.CC BY-NC · PubMed Central
Figure 3 Baicalein reduces ECAR and glycoPER. (A and B) The effect of baicalein on the mitochondrial metabolism rate was tested by OCR in KYSE150 cells. (C and D) The effect of baicalein on the glycolysis rate was tested by ECAR in KYSE150 cells. *p< 0.05.
Figure 3 Baicalein reduces ECAR and glycoPER. (A and B) The effect of baicalein on the mitochondrial metabolism rate was tested by OCR in KYSE150 cells. (C and D) The effect of baicalein on the glycolysis rate was tested by ECAR in KYSE150 cells. *p< 0.05.CC BY-NC · PubMed Central
Figure 4 Multivariate statistical analyses of samples. (A) Principal component analysis (PCA) score chart (n=2). (B) Partial least square discriminant analysis (PLS-DA) score chart. (C) variable importance in projection (VIP). (D) Expression level of metabolites treated by baicalein. (E) KEGG analysis of Differential metabolites.
Figure 4 Multivariate statistical analyses of samples. (A) Principal component analysis (PCA) score chart (n=2). (B) Partial least square discriminant analysis (PLS-DA) score chart. (C) variable importance in projection (VIP). (D) Expression level of metabolites treated by baicalein. (E) KEGG analysis of Differential metabolites.CC BY-NC · PubMed Central
Figure 5 Protein-protein interaction (PPI) network of the glycolysis-related proteins.
Figure 5 Protein-protein interaction (PPI) network of the glycolysis-related proteins.CC BY-NC · PubMed Central
Figure 6 Molecular docking of the baicalein with the core targets. (A) Molecular docking of baicalein with HK1. (B) Molecular docking of baicalein with HIF-1A.
Figure 6 Molecular docking of the baicalein with the core targets. (A) Molecular docking of baicalein with HK1. (B) Molecular docking of baicalein with HIF-1A.CC BY-NC · PubMed Central
Figure 7 Expression levels of protein and mRNA. (A) Expression levels of HIF-1A in TCGA. (B) Expression levels of HIF-1A in esophageal cancer. (C and D) Expression levels of glycolysis and cell cycle related-protein determined by Western blotting. (E) Expression levels of glycolysis and cell cycle-related mRNA by QRT-PCR. (F) The half-life of HIF-1A protein was assessed in KYSE150 cells. *p< 0.05.
Figure 7 Expression levels of protein and mRNA. (A) Expression levels of HIF-1A in TCGA. (B) Expression levels of HIF-1A in esophageal cancer. (C and D) Expression levels of glycolysis and cell cycle related-protein determined by Western blotting. (E) Expression levels of glycolysis and cell cycle-related mRNA by QRT-PCR. (F) The half-life of HIF-1A protein was assessed in KYSE150 cells. *p< 0.05.CC BY-NC · PubMed Central

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References 26 · Cited by 33

Metadata

Authors
Guo, D., Jin, J., Liu, J., Wang, Y., Li, D., & He, Y.
Affiliations
Fourth Hospital of Hebei Medical University (CN)
Corresponding author
  • Guo, Dongli
  • Jin, Jing
  • Liu, Jianghui
  • Wang, Yingying
  • Li, Daojuan
  • He, Yutong
ORCID
Venue
Drug Design, Development and Therapy
Publisher
Informa UK Limited
Published
2022-07
Volume
Volume 16
Pages
2423-2436
ISSN
1177-8881 (ISSN-L)
DOI
10.2147/dddt.s370114
PMC
PMC9346416
OpenAlex
W4288458710
Cited by
33
References
26
Citations by year
2026: 7 · 2025: 12 · 2024: 6 · 2023: 8
FWCI
3.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Drug Design Development and Therapy (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (acceptedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
Keywords
baicalein, esophageal squamous cell carcinoma, radiosensitization, radioresistance (biology), HIF1A, glycolysis, glucose metabolism, cell cycle, metabolomics, network pharmacology, molecular docking
MeSH terms
Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms, Humans, Radiation Tolerance, Flavanones, Cell Line, Tumor, Cell Proliferation, Molecular Docking Simulation

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CoChat. (2026). Citation check: Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A. https://app.cochat.ai/papers/10.2147/dddt.s370114
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Guo, D., Jin, J., Liu, J., Wang, Y., Li, D., & He, Y. (2022). Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A. Drug Design, Development and Therapy. https://doi.org/10.2147/dddt.s370114

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