N,N'-Dinitrosopiperazine–Mediated Heat-Shock Protein 70-2 Expression Is Involved in Metastasis of Nasopharyngeal Carcinoma

N,N'-Dinitrosopiperazine (DNP) is invovled in nasopharyngeal carcinoma (NPC) development and metastasis, and it shows organ specificity to the nasopharyngeal epithelium. Herein, we demonstrate that DNP induces heat-shock protein (HSP) 70-2 expression in NPC cells (6-10B) at a non-cytotoxic concentration. DNP induced HSP70-2 expression in a dose- and time- dependent manner, but showed no effect on other HSP70 family members. Furthermore, DNP also increased HSP70-2 RNA transcription through directly binding to the hypoxia-responsive elements (HRE) and heat shock elements (HSE) located in the HSP70-2 promoter. DNP-mediated HSP70-2 expression might act through enhancing the transcription of HSP70-2 RNA. Importantly, DNP induced motility and invasion of 6-10B cells dose- and time-dependently, and DNP-mediated NPC metastasis was confirmed in nude mice, which showed high HSP70-2 expression in the metastatic tumor tissue. However, the motility and invasion of NPC cells that were stably transfected using short interfering RNA against HSP70-2 could not effectively induce DNP. These results indicate that DNP induces HSP70-2 expression through increasing HSP70-2 transcription, increases the motility and invasion of cells, and promotes NPC tumor metastasis. Therefore, DNP mediated HSP70-2 expression may be an important factor of NPC-high metastasis.