Propofol enhances the sensitivity of glioblastoma cells to temozolomide by inhibiting macrophage activation in tumor microenvironment to down-regulate HIF-1α expression.
Exp Cell Res
; 418(2): 113277, 2022 09 15.
Article
en En
| MEDLINE
| ID: mdl-35810776
ABSTRACT
Temozolomide (TMZ) is the first-line drug for the clinical treatment of glioblastoma (GBM), but drug resistance limits its treatment benefits. This study was intended to investigate whether propofol could restrict the resistance of GBM cells to TMZ and uncover the underlying mechanisms. Human GBM cell line U251 and TMZ-resistant U251/TMZ cell line were transplanted into mice to construct GBM and TMZ-resistant GBM xenograft tumors. Tumor growth in mice was monitored, and the tumor tissues were collected for biochemical analysis. THP-1 cell differentiated into M0 subtype macrophage using phorbol 12-myristate 13-acetate (PMA). The culture medium of M0 macrophage was collected for treating U251 cells with the presence or absence of propofol or propofol + DMOG (HIF-1α activator). Results showed that propofol significantly enhanced the inhibitory effect of TMZ on tumor growth, macrophage infiltration and inflammation in TMZ-resistant GBM xenograft tumors in vivo. Compared with GBM xenograft tumors, higher expression of HIF-1α, O6-methylguanine-DNA methyltransferase (MGMT), p-p65 and cyclooxygenase 2 (Cox2) was observed in TMZ-resistant GBM xenograft tumors, but propofol co-treatment markedly reduced the expression of these proteins. In in vitro experiments, culture medium from M0 macrophage promoted U251 cell survival, inflammation and expression of HIF-1α, MGMT, p65 and Cox2, whereas inhibited cell apoptosis. However, propofol suppressed the PMA-induced THP-1 M0 macrophage activation, and propofol-treated culture medium from M0 macrophage blocked all the effects of M0 medium on U251 cells. Additionally, DMOG reversed the effect of propofol-treated M0 medium on U251 cells. In conclusion, Propofol restricted TMZ resistance via inhibiting macrophage activation and down-regulating HIF-1α expression in GBM.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Propofol
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Glioblastoma
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2022
Tipo del documento:
Article