RESUMO
The Notch signaling pathway plays an important role in the proliferation and differentiation of cells. Although recent studies have shown that Notch plays a role in the mechanisms of cisplatin resistance, the mechanism by which Notch plays roles in intrinsic or acquired cisplatin resistance remains unclear. In the present study, poorly differentiated nasopharyngeal carcinoma cells were treated with a γ-secretase inhibitor (DAPT), which led to a decrease in the Notch intracellular domain and inhibition of Notch signaling. Treatment was not sufficient to induce pronounced apoptosis of CNE-2 cells, but did result in the down-regulation of the P-glycoprotein and ERCC1 protein. In contrast, the combined treatment of DAPT and cisplatin induced substantial cell apoptosis compared to cisplatin treatment alone.
RESUMO
Notch signaling has been suggested to be required for many human cancers. However, the role of Notch signaling in human nasopharyngeal carcinoma cells (NPC) remains unknown. Here, we report that Notch-1, Notch-2, Notch-3 and Notch-4 are all detected in NPC cells. Notch inhibitor, GSI, suppresses the levels of Notch-1, Notch-2 and Notch-4, but not Notch-3. In addition, GSI inhibits NPC cell proliferation by inducing the cell cycle arrest and apoptosis. Furthermore, GSI inhibits the AKT and MEK signaling, without affecting P38 and JNK1/2. Thus, NPC cells may up-regulate Notch signaling to maintain cell proliferation and targeting the Notch signaling pathway may offer a potential alternative strategy for the treatment of NPC.