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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2024 21

Page:

4054-4061

Research Field:

Publishing date:

Info

Title:

In vivo and in vitro inhibitory effects of metformin on the resistance of glioblastoma cell lines to temozolomide

Author(s):

JIA Di¹; LIN Shaohui²; YUAN Ying³; LI Chenlong⁴; LI Shasha⁵; SHI Yan¹; ZHU Xinping⁶; PENG Yao¹; LI Shuyan¹

Keywords:

glioblastoma; metformin; temozolomide; drug resistance

PACS:

R739.41

DOI:

10.3969/j.issn.1672-4992.2024.21.007

Abstract:

Objective:To explore the inhibitory effect and molecular mechanism of metformin on temozolomide(TMZ) resistance in glioblastoma (GBM),and provide theoretical foundation for clinical application of metformin in the treatment of GBM resistance.Methods:CCK-8 assay was used to detect the effect of metformin on the chemosensitivity of GBM drug-resistant cells.Flow cytometry was used to detect the effect of metformin on the apoptosis rate of GBM drug-resistant cells.Colony formation assay,nude mouse tumorigenesis assay,scratch assay,Transwell invasion assay and neurosphere formation assay were used to detect the effect of metformin on the colony formation ability,tumorigenic ability,migration ability,invasion ability and stem cell characteristics of GBM drug-resistant cells.Triglyceride content detection kits were used to detect the changes of triglyceride in parental cells and GBM drug-resistant cells before and after metformin administration.RT-PCR and Western Blot were used to detect the role of SREBP1 gene and protein expression in the parental cells and GBM drug-resistant cells before and after metformin administration.Results:Metformin treatment could significantly enhance the sensitivity of LN229-R and U251-R to TMZ,and increase the apoptosis rate of drug-resistant cells to TMZ.Metformin could reduce the colony formation ability,the tumor-forming ability in vivo,the migration and invasion ability,the characteristics of tumor stem cells,and the triglyceride content of GBM resistant cells£¨P all£¼0.05£©.Metformin could reduce the expression of SREBP1 mRNA and protein level£¨P all£¼0.05£© in resistant cells.SREBP1 suppression reversed TMZ resistance of resistant cells £¨P£¼0.05£©,while metformin did not cause significant inhibition in SREBP1-knockdown resistant cells£¨P£¾0.05£©.Conclusion:Metformin treatment reduced the colony formation,proliferation,migration,invasion and tumor stem cell properties of GBM resistant cell lines,and increased the apoptosis rate of GBM resistant cells to TMZ.Metformin may reduce triglyceride content in GBM-resistant cells by inhibiting SREBP1,thus inhibiting the drug resistance of GBM to TMZ.

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Last Update: 2024-09-30