Programmed cell death via apoptosis is associated with a ser

Programmed cell death via apoptosis is associated with a series of morphological and biochemical characteristics, including cell shrinkage, the rapid increase of intracellular calcium, nuclear condensation, DNA fragmentation and the formation of apoptotic bodies. Known as a shared feature of most apoptotic cells, cell shrinkage or a decrease in cell volume is referred to as decreased apoptotic volume (apoptotic volume decrease, AVD). AVD is regarded as an early triggering factor for apoptosis as it emerges earlier than the release of cytochrome C, the activation of cysteine aspartic protease (cysteine-containing aspartate-specific proteases, caspase-3) and DNA fragmentation. Therefore, in the last decade, ion channels which contribute to cell volume regulation after osmotic cell swelling, have an important role in AVD. Cl− channels triggered with apoptosis inducers exhibit electrophysiological properties similar to those of VSOR Cl− channels. VSOR Cl− currents are activated in mitochondria and by death receptor-mediated apoptosis, while VSOR Cl− channel blockers (NPPB and DIDS) block these currents and can reverse apoptosis in tumor Cy5 maleimide (non-sulfonated) and T cells [34]. In accordance with previous data, we found that VSOR Cl− channels play a very important role in the proliferation of human NPCs, apoptosis in human lung adenocarcinoma cells [35]. These results suggest that VSOR Cl− channels are engaged in proliferation, metastasis and apoptosis in tumor cells. The ClC-3 chloride channel is a member of the voltage-dependent chloride channel family. When cell volume increases, the ClC-3 channel is activated, and Cl− efflux, which forms a chloride current, mediates the transport of substances, induces the release of intracellular organic matter and regulates cell volume. The ClC-3 channel protein is associated with cell proliferation, differentiation and apoptosis. However, the molecular mechanisms by which VSOR Cl− channels are regulated are not clear. The VSOR Cl− channel protein is thought to be a P-glycoprotein (P-glycoprotein, P-gP), like ClC-3 and ClC-2, and to influence cell apoptosis by taking part in the regulation of cell volume. The VSOR Cl− channel mediates the transmembrane transport of chloride ions to regulate AVD. Whereas it would be worthwhile to study whether this channel partakes in GNA-induced apoptosis of CNE-2Z cells, GNA was used to induce apoptosis in CNE-2Z cells in this study. The cells were treated with blocking agents (DIDS, DCPIB), and the survival rate, apoptosis and apoptosis rate were detected by MTT, DAPI staining and flow cytometry assays, respectively. We found that the chloride channel blockers (DIDS and DCPIB) effectively reduced CNE-2Z-induced apoptosis in GNA cells. Then, the CLC-3 gene was silenced by an siRNA in CNE-2Z cells. The results revealed that after the CLC-3 gene was silenced, cell apoptosis varied in a manner similar to that observed in blocker-treated CNE-2Z cells. Hence, in CNE-2Z cells induced by GNA, apoptosis may be related to the activation of VSOR Cl− channels, but the mechanism underlying this effect requires further exploration.