Morphine protects SH-SY5Y human neuroblastoma cells against Dickkopf1-induced apoptosis.

Abstract

Morphine is used to relieve pain in patients with cancer in terminal phases. Dickkopf‑1 (DKK1), a secreted protein, is a negative regulator of the Wnt/β‑catenin signaling pathway. Morphine and DKK1 are associated with tumorigenesis. However, to the best of our knowledge, there is no study evaluating the effects of these two factors simultaneously. In the present study, the effects of morphine and DKK1 on neuroblastoma cells invivo and invitro were evaluated. To establish the invitro effects of DKK1 and morphine, human neuroblastoma SH‑SY5Y cells were transfected with a DKK1‑expressing plasmid and cell migration, apoptosis, migration and invasion were evaluated prior to and following morphine treatment. The results indicated that DKK1 induced apoptosis and inhibited the mobility of neuroblastoma cells and that morphine attenuated these DKK1‑induced effects. To evaluate the effects of DKK1 and morphine invivo, a mouse model of neuroblastoma was established, where mice bearing tumors of native SH-SY5Y cells were injected with DKK1. Tumor size, spatial memory and survival rate were investigated in untreated, DKK1‑treated and DKK1+morphine‑treated mice. Water maze and T‑maze tests were performed, which revealed that DKK1‑treated mice exhibited a better memory than DKK1+morphine‑treated mice. The expression of DKK1 in established xenografted tumors was associated with decreased tumor size and an increased survival rate, whereas morphine reversed these effects. Furthermore, it was confirmed that morphine and DKK1 take effect, at least in part, via the Wnt/β‑catenin signaling pathway. The results of the present study indicate that morphine may protect neuroblastoma cells and thus, it may be used in neuroblastoma patients.