PPARβ/δ Agonist GW501516 Inhibits Tumorigenicity of Undifferentiated Nasopharyngeal Carcinoma in C666-1 Cells by Promoting Apoptosis

Frontiers in Pharmacology
Yangyang JiLinglan Gu

Abstract

Activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) had been linked to inhibition on the proliferation and apoptosis in a few cancer cell lines. However, limited data exists regarding the role of PPARβ/δ in nasopharyngeal carcinoma (NPC). This study was undertaken to determine the effect of PPARβ/δ on cell proliferation, anchorage-dependent clonogenicity, and ectopic xenografts in the human NPC cell lines. Gene and protein expression of PPARβ/δ were reduced specifically in the poor- and un-differentiated NPC cell lines as compared with the control NP-69 cells. Ligand activation of PPARβ/δ by GW501516, a specific PPARβ/δ selective agonist, inhibited cell proliferation and colony formation strikingly, and induced a G2/M phase arrest in the EBV positive undifferentiated NPC C666-1 cells relative to the control cells. Moreover, GW501516 induced C666-1 cell apoptosis in a caspase and BAX dependent manner. In accordance with the in vitro result, GW501516 significantly suppressed the ectopic NPC xenograft tumorigenicity that derived from the C666-1 NPC cells in BALB/c nu/nu mice. This effect is greatly associated with its inhibition on the gene and protein expression of integrin-linked kinase (ILK) through activatio...Continue Reading

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Citations

Jul 8, 2020·Nature Reviews. Endocrinology·Sean L McGee, Mark Hargreaves
Aug 17, 2020·Archives of Physiology and Biochemistry·Dan LiuBokui Xiao
May 8, 2020·Cells·Nicole Wagner, Kay-Dietrich Wagner
May 3, 2019·Pharmacology & Therapeutics·Tanweer HaiderVandana Soni

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Methods Mentioned

BETA
xenograft
fluorescence microscopy
PCR
Assay
flow cytometry
Protein Assay
transfection
xenografts

Software Mentioned

SPSS

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