Zoledronic acid reverses cisplatin resistance in nasopharyngeal carcinoma cells by activating the mitochondrial apoptotic pathway.

Despite improvements to radiotherapeutic strategies, resistance to adjuvant chemotherapy remains the main problem underlying the low 5-year survival rate in patients with nasopharyngeal carcinoma (NPC). In the present study, the human NPC cell line HNE1 was exposed to gradually increasing concentrations of cisplatin (CDDP) in order to establish a drug-resistant sub-cell line, HNE1/CDDP. HNE1/CDDP cells exhibited multidrug resistance and a prolonged doubling time, as compared with the parent HNE1 cells. Furthermore, pretreatment with zoledronic acid (ZOL) appeared to resensitize the CDDP-resistant cells by inducing S-phase cell cycle arrest and the mitochondrial apoptotic pathway by upregulating the expression of B-cell lymphoma-2 (BCL-2)-associated X protein and caspase-9 and downregulating the expression of BCL-2. The results of the present study suggested that HNE1/CDDP cells are a stable, multidrug-resistant NPC cell line that may serve as an important tool for research in drug resistance. In addition, the application of ZOL may hold clinical therapeutic potential for the treatment of drug resistance in NPC.