title: PI3K Inhibitor Combined With Chemotherapy Can Enhance the Apoptosis of Neuroblastoma Cells In Vitro and In Vivo.
abstract: Activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is a novel poor prognostic indicator of neuroblastoma (NB), and the positive effects of chemotherapy on NB have been confirmed. In this study, we investigated the effect of small molecule PI3K inhibitor PI103 on chemosensitivity. The PI3K inhibitor cooperates with doxorubicin to synergistically induce apoptosis and to reduce tumor growth of NB in in vitro and in vivo models. Human NB cells, SH-SY5Y and SK-N-BE(2), were treated with PI103 combined doxorubicin-enhanced Bid cleavage, activated Bax, and caspase 3. Activation of caspase 3 was also observed in xenografts of NB in nude mice upon combination of doxorubicin with the specific PI3K inhibitor PI103. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Both PI103 and doxorubicin inhibited growth of NB in vitro and PI103 induced a G1 arrest of NB cells. PI103 combined doxorubicin significantly inhibits the growth of established NB tumors, induced apoptosis of tumor cells, and improved the survival of mice in vivo Taken together, our findings suggest that PI3K inhibition seems to be a promising option to sensitize tumor cells for chemotherapy in NB, which may be effective in the treatment of NBs.
authors.affiliation: Department of General Surgery, Children's Hospital of Zhengzhou, Henan, China.
authors.forename: Xianjie
authors.initials: X
authors.lastname: Geng
authors.affiliation: Division of Surgery, Hospital of Chinese Medicine, Zhangqiu, Shandong, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Neurosurgery, People's Hospital of Weifang, Shandong, China xinghongshun@163.com.
authors.forename: Hongshun
authors.initials: H
authors.lastname: Xing
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D006801:Humans; D051379:Mice; D000071447:N-Myc Proto-Oncogene Protein / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D000071447:N-Myc Proto-Oncogene Protein; C522973:PI103; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D004317:Doxorubicin; D058570:TOR Serine-Threonine Kinases
keywords: Dox; PI103; PI3K inhibitor; apoptosis; neuroblastoma