Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y2-receptors

Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antiproliferative effects of P2-purinergic receptors in human oesophageal cancer cells, Prolonged incubation of primary cell cultures of human oesophageal cancers as welt-as of the squamous oesophageal cancer cell line Kyse-140 with ATP or its stable analogue ATPgammaS dose-dependently inhibited cell proliferation, This was due to both an induction of apoptosis and cell cycle arrest The expression of P2-receptors was examined by RTPCR, immunocytochemistry, and [Ca2+](i)-imaging. Application of various extracellular nucleotides dose-dependently increased [Ca2+](i), The rank order of potency was ATP=UTP > ATPgammaS > ADP=UDP. 2-methylthio-ATP and xbeta-methylene-ATP had no effects on [Ca2+], Complete cross-desensitization between ATP and UTP was observed. Moreover. the phospholipase C inhibitor U73122 dose-dependently reduced the ATP triggered [Ca2+], signal, The pharmacological features strongly suggest the functional expression of G-protein coupled P2Y(2)-receptors in oesophageal squamous cancer cells. P2Y(2)-receptors are involved in the antiproliferative actions of extracellular nucleotides. Thus, P2Y(2)-receptors are promising target proteins for innovative approaches in oesophageal cancer therapy.