title: 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 in vivo and in vitro were evaluated. To establish the in vitro 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 in vivo, 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.
authors.affiliation: Department of Anaesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Kun-Peng
authors.initials: KP
authors.lastname: Wang
authors.affiliation: Department of Anaesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Anaesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anaesthesiology, Shenzhen Hospital, Shenzhen, Guangdong 518000, P.R. China.
authors.forename: Jin-Zhen
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D014183:Transplantation, Heterologous; D051176:beta Catenin / Q000378:metabolism
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D009294:Narcotics; D051176:beta Catenin; D009020:Morphine