Anti-tumor effects of telmisartan in glioma-astrocyte non-contact co-cultures: A critical role of astrocytic IL-6-mediated paracrine growth promotion.
Int Immunopharmacol
; 139: 112707, 2024 Sep 30.
Article
in En
| MEDLINE
| ID: mdl-39032472
ABSTRACT
Telmisartan, an angiotensin II type 1 receptor (AT1R) blocker, exhibits broad anti-tumor activity. However, in vitro, anti-proliferative effects are shown at doses far beyond the therapeutic plasma concentration. Considering the role of tumor microenvironment in glioma progression, glioma-astrocyte co-cultures were employed to test the anti-tumor potential of low-dose telmisartan. When a high dose was required for a direct anti-proliferative effect on glioma cell lines, a low dose significantly inhibited glioma cell proliferation and migration in the co-culture system. Under co-culture conditions, upregulated IL-6 expression in astrocytes played a critical role in glioma progression. Silencing IL-6 in astrocytes or IL-6R in glioma cells reduced proliferation and migration. Telmisartan (5 µM) inhibited astrocytic IL-6 expression, and its anti-tumor effects were reversed by silencing IL-6 or IL-6R and inhibiting signal transducer and activator of transcription 3 (STAT3) activity in glioma cells. Moreover, the telmisartan-driven IL-6 downregulation was not imitated by losartan, an AT1R blocker with little capacity of peroxisome proliferator-activated receptor-gamma (PPARγ) activation, but was eliminated by a PPARγ antagonist, indicating that the anti-glioma effects of telmisartan rely on its PPARγ agonistic activity rather than AT1R blockade. This study highlights the importance of astrocytic IL-6-mediated paracrine signaling in glioma growth and the potential of telmisartan as an adjuvant therapy for patients with glioma, especially those with hypertension.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Astrocytes
/
Interleukin-6
/
Coculture Techniques
/
PPAR gamma
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Angiotensin II Type 1 Receptor Blockers
/
Cell Proliferation
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STAT3 Transcription Factor
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Telmisartan
/
Glioma
Limits:
Humans
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China