Cisplatin-based concomitant chemoradiotherapy is considered as the standard treatment for locally advanced nasopharyngeal carcinoma patients. However, the curative efficacy of cisplatin-based chemotherapy is limited because of the occurrence of cisplatin resistance. Some researches indicate that activating the volume-sensitive Cl− channel might be a new strategy for the reduction of cisplatin resistance. However, little is known about the activation pathway of the Cl− channels activated by cisplatin. In this study, the cisplatin-activated chloride current was investigated using the whole cell patch-clamp technique in the poorly differentiated nasopharyngeal carcinoma cells (CNE-2Z cells), and the activation pathway of the current was also discussed. The results showed that extracellular application of cisplatin activated a Cl− current, showing the properties of significant outward rectification, intracellular ATP dependency, and a selectivity sequence of I− > Br− > Cl− > gluconate, and being inhibited by the Cl− channel inhibitors tamoxifen and extracellular ATP. These characteristics are similar to those of the volume-sensitive Cl− current in CNE-2Z cells, indicating that cisplatin induces the Cl− current by activating the volume-sensitive like chloride channel. The cisplatin-activated current was blocked by suramin (a wide-spectrum purinergic antagonist) and RB2 (a relatively selective P2Y antagonist). In addition, the current was depressed by extracellular application of apyrase. The apoptotic volume decrease induced by cisplatin was also attenuated by RB2. P2Y receptors were expressed in CNE-2Z cells. These results suggest that cisplatin can induce a Cl− current by activating volume-sensitive like Cl− channels through the P2Y purinoceptor pathway.
The Journal of Membrane Biology – Springer Journals
Published: Sep 19, 2014
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