Silibinin down-regulates PD-L1 expression in nasopharyngeal carcinoma by interfering with tumor cell glycolytic metabolism Journal Article

   

Authors:	Sellam, L. S.; Zappasodi, R.; Chettibi, F.; Djennaoui, D.; Yahi-Ait Mesbah, N.; Amir-Tidadini, Z. C.; Touil-Boukoffa, C.; Ouahioune, W.; Merghoub, T.; Bourouba, M.
Article Title:	Silibinin down-regulates PD-L1 expression in nasopharyngeal carcinoma by interfering with tumor cell glycolytic metabolism
Abstract:	The upregulation of checkpoint inhibitor PD-L1 expression has recently been associated with nasopharyngeal carcinoma (NPC) resistance to therapy. The mechanism of induction of PD-L1 has also been linked to enhanced aerobic glycolysis promoted by HIF1-α dysregulation and LDH-A activity in cancer. Here, we investigated the effect of the anti-tumoral compound Silibinin on HIF-1α/LDH-A mediated cancer cell metabolism and PD-L1 expression in NPC. Our results demonstrate that exposure to Silibinin potently inhibits tumor growth and promotes a shift from aerobic glycolysis toward oxidative phosphorylation. The EBV + NPC cell line C666-1 and glycolytic human tumor explants treated with Silibinin displayed a reduction in LDH-A activity which consistently associated with a reduction in lactate levels. This effect was accompanied by an increase in intracellular citrate levels in C666-1 cells. Accordingly, expression of HIF-1α, a critical regulator of glycolysis, was down-regulated after treatment. This event associated with a down-regulation in PD-L1. Altogether, our results provide evidence that silibinin can alter PD-L1 expression by interfering with HIF-1α/LDH-A mediated cell metabolism in NPC. These results provide a new perspective for Silibinin use to overcome PD-L1 mediated NPC resistance to therapy. © 2020 Elsevier Inc.
Keywords:	adult; clinical article; controlled study; human tissue; human cell; drug efficacy; antineoplastic agent; drug inhibition; antineoplastic activity; drug potency; in vitro study; drug effect; enzyme activity; explant; cancer inhibition; citric acid; nasopharynx carcinoma; down regulation; hypoxia inducible factor 1alpha; cell metabolism; oxidative phosphorylation; concentration response; programmed death 1 ligand 1; antiproliferative activity; glucose metabolism; pd-l1; hif-1α; aerobic glycolysis; npc; silibinin; human; priority journal; article; lactate dehydrogenase a; ldh-a; c666-1 cell line
Journal Title:	Archives of Biochemistry and Biophysics
Volume:	690
ISSN:	0003-9861
Publisher:	Elsevier Inc.
Date Published:	2020-09-15
Start Page:	108479
Language:	English
DOI:	10.1016/j.abb.2020.108479
PUBMED:	32679194
PROVIDER:	scopus
PMCID:	PMC8507490
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85088123716&doi=10.1016%2fj.abb.2020.108479&partnerID=40&md5=2880fead15029bb975828fc4f61d0b4a
Notes:	Article -- Export Date: 3 August 2020 -- Source: Scopus

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