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Study on the Mechanism of Temozolomide Resistance in Glioma under Hypoxic Microenvironment
1.903 Hospital， Sichuan Jiangyou 621700， China；
2.Pu'er People's Hospital， Yunnan Pu'er 665000， China
Received date: 2025-07-24
Revised date: 2025-09-01
Accepted date: 2026-04-20
Online published: 2026-04-21
Objective： To observe the effect of temozolomide on the phenotype of glioma cells in hypoxic microenvironment and to explore the mechanism of temozolomide resistance of glioma cells in hypoxic microenvironment.Methods： ①To construct a hypoxic microenvironment： The T98G cells were set as the normoxia group （21% oxygen content） and the hypoxia group （1% oxygen content）. After the cells adhered， 1 mmol·L-1 temozolomide （TMZ） was added to the two groups of cells. After 72 h of culture， the cell proliferation was detected by CCK-8 assay， and the cell migration and invasion were detected by cell scratch and transwell assay. The expressions of hypoxia-inducible factor-1α （HIF-1α） and transforming growth factor-β1 （TGF-β1） in the two groups were detected by western blot. ② Interfere with the expression of HIF-1α in T98G cells： After the cells of the interference group （sh-HIF-1α） and the blank control group （sh-control） were cultured in 1% hypoxic microenvironment to adhere to the cell wall， 1mmol·L-1 temozolomide was added to the two groups of cells， and continued to culture for 72 h， and the changes of cell proliferation， migration， invasion ability， and the expression level of TGF-β1 were analyzed.Results： ①The proliferation， migration and invasion of glioma cells in the hypoxia group were higher than those in the normoxia group （P<0.05）. The expression levels of HIF-1α and TGF-β1 in glioma cells in the hypoxia group were higher than those in the normoxia group （P<0.05）. ②The proliferation and migration abilities of T98G cells in the HIF-1αinterference group were lower than those in the blank control group （P<0.05）， and the TGF-β1 expression level of T98G cells in the HIF-1αinterference group was also lower than that in the blank control group （P<0.05）.Conclusion： Hypoxic microenvironment can attenuate the effects of temozolomide on the proliferation， migration and invasion of glioma cells. Hypoxic microenvironment may promote the chemoresistance of glioma cells by up-regulating the expression of HIF-1α and TGF-β1. HIF-1α may be involved in the drug resistance of glioma cells through mediating TGF-β1 under hypoxic microenvironment.
Key words： ; Glioma； ; Temozolomide ; （TMZ）； ; Hypoxia； ; Microenvironment； ; Drug resistance
ZHAO Jinyang, XU Zhixing, CHEN De
.
Study on the Mechanism of Temozolomide Resistance
in Glioma under Hypoxic Microenvironment
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