title: Inhibition of δ-opioid receptors induces brain glioma cell apoptosis through the mitochondrial and protein kinase C pathways.
abstract: Brain glioma is a malignant tumor with a high incidence rate and poor prognosis that has become a focus of studies of central nervous system diseases. Previous studies have suggested that δ-opioid receptors may affect the proliferation and apoptosis of numerous types of tumor cells. However, to date, their precise mechanism(s) of action have not been elucidated. The present study aimed to investigate the effects of inhibiting δ-opioid receptors in brain glioma cell proliferation and apoptosis and their relevant molecular mechanisms. Various doses of naltrindole were supplied to treat brain glioma cells using the MTT method to assess the proliferation index. Flow cytometry was used to investigate the changes in cell apoptosis and mitochondrial membrane potential. The expression levels of Bax, Bcl-2, Bcl-xL, cytochromec, caspase-9, caspase-3 and protein kinase C (PKC) were measured using western blotting. Naltrindole was observed to inhibit brain glioma cell proliferation and promote apoptosis in a dose- and time-dependent manner. Furthermore, the addition of naltrindole lead to changes in the brain glioma cell membrane potential and regulated Bax translocation to the mitochondrial membrane, consequently promoting the release of cytochromecinto the cytoplasm, followed by the activation of caspase-9 and -3, which caused cell apoptosis. In addition, naltrindole was able to regulate the expression levels of the cellular internal phosphorylated PKC proteins, which are closely associated with the inhibition of cell proliferation. In conclusion, the inhibition of δ-opioid receptors may inhibit brain glioma cell proliferation and lead to apoptosis, which is closely associated with the mitochondrial and PKC pathways.
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Zhou
authors.forename: Xudong
authors.initials: X
authors.lastname: Guo
authors.forename: Mo
authors.initials: M
authors.lastname: Chen
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Fu
authors.forename: Jingbin
authors.initials: J
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.forename: Zirong
authors.initials: Z
authors.lastname: Yang
authors.forename: Wenhai
authors.initials: W
authors.lastname: Fan
keywords: apoptosis; glioma; mitochondria; protein kinase C pathway; δ-opioid receptor