(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
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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 |
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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 |
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