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3D Microfluidic System for Evaluating Inhibitory Effect of Chinese Herbal Medicine Oldenlandia diffusa on Human Malignant Glioma Invasion Combined with Network Pharmacology Analysis

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Abstract

Objective

To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD).

Methods

The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach.

Results

Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization.

Conclusions

]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.

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Authors and Affiliations

  1. Stem Cells Clinical Research Institution, the First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning Province, China

    Chun-hui Han, Jing-yun Ma, Na Li &  Jing Liu

  2. Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, 116023, Liaoning Province, China

    Chun-hui Han, Jing-yun Ma, Wei Zou, Guo Jin &  Jing Liu

  3. Integrated Chinese and Western Medicine Laboratory, the First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning Province, China

    Jia-lin Qu

  4. Department of Traditional Chinese Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning Province, China

    Yang Du, Yong Liu & Ai-jing Leng

Authors
  1. Chun-hui Han
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  2. Jing-yun Ma
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  3. Wei Zou
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  4. Jia-lin Qu
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  6. Na Li
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  10. Jing Liu
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Contributions

Han CH conducted the design and the main experiments of this study and drafted the manuscript. Ma JY designed the microfluidic chip and directed this part of the experiment. Zou W supervised the writing of the thesis. Qu JL directed and participated in the UPLC-Q-TOF/MS experiment. Du Y participated in the exploration of UPLC experimental conditions. Li N participated in the experiment of 3D cells perfusion culture on microfluidic chips. Liu Y took part in the design of the CM experiment in this study. Jin G participated in the revision of the article. Leng AJ participated in the extraction and analysis of the herb and the promotion of the project. Liu J led the design of the study and promotion of the project. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jing Liu.

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The authors declare no conflicts of interest.

Additional information

Supported by the National TCM Characteristic Technology Inheritance Talent Training Program (National TCM Education Letter [2019]43, No. J20194828003)

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11655_2021_3726_MOESM1_ESM.pdf

3D Microfluidic System for Evaluating the Inhibitory Effect of Chinese Herbal Medicine Oldenlandiadiffusaon Human Malignant Glioma Invasion Combined with Network Pharmacology Analysis

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Han, Ch., Ma, Jy., Zou, W. et al. 3D Microfluidic System for Evaluating Inhibitory Effect of Chinese Herbal Medicine Oldenlandia diffusa on Human Malignant Glioma Invasion Combined with Network Pharmacology Analysis. Chin. J. Integr. Med. 29, 52–60 (2023). https://doi.org/10.1007/s11655-021-3726-1

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  • DOI: https://doi.org/10.1007/s11655-021-3726-1

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