PPAR gamma Agonist, Pioglitazone, Suppresses Melanoma Cancer in Mice by Inhibiting TLR4 Signaling

(2019) PPAR gamma Agonist, Pioglitazone, Suppresses Melanoma Cancer in Mice by Inhibiting TLR4 Signaling. Journal of Pharmacy and Pharmaceutical Sciences. pp. 418-427. ISSN 1482-1826

Full text not available from this repository.

Official URL: WOS:000487106200001

Abstract

Background: Although previous studies demonstrated an anticancer effect for the ligands of peroxisome proliferator-activated receptor gamma (PPAR gamma) through activation of its anti-inflammatory responses, nevertheless the anti-tumor mechanism of PPAR gamma has not been intensively investigated. One of the molecules involved in cancer progression is toll-like receptor 4 (TLR4). TLR4 signaling induces NF-kappa B activity which has a crucial role in cancer progression. In this study, we examined the cross-talk between PPAR gamma and TLR4 in the melanoma. Methods: B16F10 melanoma cells were cultured with or without LPS for 24 hr. The cells were subcutaneously injected to two groups of C57BL/6 mice. After the development of palpable tumors each group of animals were divide to four sub-groups and received pioglitazone in different dose ranges (0,10,50,100 mg/kg/day) for 10 days. At the end of the study, the expression of Tlr4, Myd-88, Nf-kb1 genes was evaluated by qRT-PCR in different groups in mice tumor. The TLR-alpha protein expression was evaluated by IHC. TNF-alpha level in mice tumor and serum were measured by ELISA kits. Tumor volume was measured with Vernier calipers. Results: We observed that activation of PPAR gamma by its agonist, pioglitazone, reduces tumor volume, Tlr-4, Myd-88, Nf-kb1 mRNA expression, TLR4 protein expression and TNF-alpha production in melanoma tumor especially in groups that were injected with LPS -stimulated cells. Moreover, treatment of melanoma cells with pioglitazone showed that the inhibitory effects of pioglitazone on LPS-induced inflammatory responses were TLR4 dependent. Conclusion: The results indicate that pioglitazone, a PPAR gamma agonist, has a beneficial protective effect against melanoma via interfering with the TLR4-dependent signaling pathways.

Item Type: Article
Keywords: activated-receptor-gamma nf-kappa-b lps-induced inflammation toll-like receptors cell-growth map kinase in-vitro expression alpha toll-like-receptor-4 Pharmacology & Pharmacy
Subjects: QZ Pathology > QZ 200-380 Neoplasms
Divisions: Cardiovascular Research Institute > Applied Physiology Research Center
Cardiovascular Research Institute > Isfahan Cardiovascular Research Center
Faculty of Medicine > Department of Basic Science > Department of Physiology
Page Range: pp. 418-427
Journal or Publication Title: Journal of Pharmacy and Pharmaceutical Sciences
Journal Index: ISI
Volume: 22
Identification Number: https://doi.org/10.18433/jpps30626
ISSN: 1482-1826
Depositing User: Zahra Otroj
URI: http://eprints.mui.ac.ir/id/eprint/10963

Actions (login required)

View Item View Item