MEDIX, God. 14 Br. 75/76  •  Stručni članak  •  Onkologija HR ENG

Potencijalni antitumorski učinci PPARγThe potential role of PPARγ in cancer therapy

Marina Gradišer, Martina Matovinović

Peroksisom proliferator aktivirani receptor gamma (PPARγ) pripada obitelji nuklearnih hormonskih receptora (NHR) i ligandom je aktivirani transkripcijski faktor koji neposredno regulira transkripciju ciljnih gena. Prirodni ligandi su mu metaboliti arahidonske kiseline, prostanglandini, masne kiseline dobivene oksidacijom lipoproteina niske gustoće (oxLDL), a sintetski antidijabetički lijekovi glitazoni i nesteroidni protuupalni lijekovi. Roziglitazon je oralni hipoglikemik koji se u kliničkoj praksi upotrebljava za liječenje dijabetesa tipa 2, ima visok afinitet za PPARγ receptore, a povećava inzulinsku osjetljivost. Aktivacija PPARγ receptora sudjeluje u diferencijaciji adipocita, regulaciji metabolizma glukoze, modulaciji upalnog odgovora i angiogenezi. Nedavno je dokazana PPARγ ekspresija u humanim somatotropinomima, a njihova stimulacija može kontrolirati transkripciju, sekreciju i apoptozu tih adenoma. PPARγ posjeduje potencijalno antineoplastičko djelovanje na solidne tumore, ali i leukemije putem inhibicije stanične proliferacije, indukcije apoptoze i terminalne diferencijacije kao i inhibicije angiogeneze. PPARγ ligandi predstavljaju novi, obećavajući terapijski pristup za određene vrste malignoma

Ključne riječi:
PPAR, roziglitazon, adenom hipofize, dijabetes melitus

Članak u cijelosti pročitajte u tiskanom izdanju MEDIX, God. 14 Br. 75/76

Peroxisomal proliferator activated receptor gamma (PPARgamma) belongs to the family of nuclear hormone receptors (NHRs), which directly regulate transcription of target genes. Its natural ligands are arachidonic acid metabolites, prostaglandines, low density lipoproteins oxidation (oxLDL) derivated fat acids while its sintetic ligands are antidiabetic drugs - glitazones and nonsteroid antiinflamatory drugs. Rosiglitazone has been widely used in clinical practice as an oral antidiabetic agent for the treatment of diabetes mellitus and disturbed lipid metabolism in patients with type 2 diabetes mellitus and obesity. It also improves insulin sensitivity and glucose homeostasis in patients with impaired glucose tolerance. Activation of PPARγ is involved in adipocyte differentiation process, glucose metabolism, inhibition of inflammatory response, and anti-angiogenesis. Recently, abundant expression of this receptor was demostrated in human PRL- and GH-secreting and non-functioning pituitary tumors, as well as inhibition of tumor growth and hormonal activity in vivo and in vitro by PPARγ ligands. PPARγ has potential antineoplastic effect on solid cancers, but also on leucaemia by inhibiting cell proliferation, apoptosis induction and terminal differentiation as well as angiogenesis inhibition. PPARγ ligands represent a novel promising therapeutic approach for certain types of malignancy.

Key words:
PPARγ, rosiglitazone, pituitary adenoma, diabetes mellitus