RESEARCH ARTICLE Inhibition of Autophagy Potentiated the Antitumor Effect of Nedaplatin in Cisplatin- Resistant Nasopharyngeal Carcinoma Cells

Nedaplatin, a cisplatin analog, was developed to reduce the toxicity of cisplatin, whereas it can be cross-resistant with cisplatin in some circumstances. This study aimed to investi-gate the role of autophagy in nedaplatin induced cell death in cisplatin-resistant nasopha-ryngeal carcinoma cells. Here, we showed that HNE1/DDP and CNE2/DDP cells were resistant to nedaplatin-induced cell death with reduced apoptotic activity. Nedaplatin treat-ment resulted in autophagosome accumulation and increased expression of LC3-II, indicating the induction of autophagy by nedaplatin in HNE1/DDP and CNE2/DDP cells. Inhibition of autophagy by Bafilomycin A1 (Baf A1) and 3-Methyladenine (3-MA) remarkably enhanced the antitumor efficacy of nedaplatin in HNE1/DDP and CNE2/DDP cells, suggest-ing that the resistance to nedaplatin-induced cell death was caused by enhanced autop-hagy in nedaplatin-resistant NPC cells. Additionally, Baf A1 enhanced reactive oxygen species (ROS) generation and apoptosis induced by nedaplatin in HNE1/DDP cells. Mech-anistically, nedaplatin treatment caused activation of ERK1/2 and suppression of Akt/ mTOR signaling pathways. While inhibition of ERK1/2 by MEK1/2 inhibitor, U0126, coul