2. Academic Validation
  3. Effect of luteolin on glioblastoma's immune microenvironment and tumor growth suppression

Effect of luteolin on glioblastoma's immune microenvironment and tumor growth suppression

  • Phytomedicine. 2024 May 10:130:155611. doi: 10.1016/j.phymed.2024.155611.
Shengliang Zong 1,  Xinqiao Li 1,  Guoqing Zhang 1,  Jinpeng Hu 1,  Hao Li 1,  Zhengting Guo 1,  Xiang Zhao 1,  Junhua Chen 1,  Yongfeng Wang 2,  Zhitao Jing 3
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang, Liaoning Province 110001, China.
  • 2 Department of Radiology, The First Hospital of China Medical University, No.155, Nanjing North Street, Heping District, Shenyang, Liaoning Province 110001, China. Electronic address: wyf1208@163.com.
  • 3 Department of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang, Liaoning Province 110001, China. Electronic address: jingzhitao@hotmail.com.
PMID: 38776737 DOI: 10.1016/j.phymed.2024.155611
Abstract

Background: Glioblastoma is the most malignant and prevalent primary human brain tumor, and the immunological microenvironment controlled by glioma stem cells is one of the essential elements contributing to its malignancy. The use of medications to ameliorate the tumor microenvironment may give a new approach for glioma treatment.

Methods: Glioma stem cells were separated from clinical patient-derived glioma samples for molecular research. Other studies, including CCK8, EdU, Transwell, and Others, supported luteolin's ability to treat glioma progenitor cells. Network pharmacology and molecular docking models were used to study the drug target, and qRT-PCR, WB, and IF were used to evaluate the molecular mechanism. Intracranial xenografts were examined using HE and IHC, while macrophage polarization was examined using FC.

Results: We originally discovered that luteolin inhibits glioma stem cells. IL6 released by glioma stem cells is blocked during medication action and inhibits glioma stem cell proliferation and invasion via the IL6/STAT3 signaling pathway. Additionally, luteolin inhibits the secretion of TGFβ1, affects the polarization function of macrophages in the microenvironment, inhibits the polarization of M2 macrophages in TAM, and further inhibits various functions of glioma stem cells by affecting the IL6/STAT3 signaling pathway, luteolin crosstalk TGFβ1/SMAD3 signaling pathway, and so on.

Conclusions: Through the suppression of the immunological microenvironment and inhibition of the IL6/STAT3 signaling pathway, our study determined the inhibitory effect of luteolin on glioma stem cells. This medication's dual inhibitory action, which has a significant negative impact on the glioma stem cells' malignant process, makes it both a viable anti-glioma medication and a candidate for targeted glioma microenvironment therapy.

Keywords

Glioblastoma; Glioma stem cells; Immunological microenvironment; Luteolin; Macrophage.

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