PI3K Inhibitor Combined With Chemotherapy Can Enhance the Apoptosis of Neuroblastoma Cells In Vitro and In Vivo
| Autor: | Hongshun Xing, Xianjie Geng, Lingling Xie |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Survival Pyridines medicine.medical_treatment Antineoplastic Agents Apoptosis Biology Neuroblastoma cell 03 medical and health sciences Mice Neuroblastoma 0302 clinical medicine In vivo Cell Line Tumor medicine Animals Humans Furans Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Chemotherapy N-Myc Proto-Oncogene Protein Akt/PKB signaling pathway TOR Serine-Threonine Kinases Cell Cycle medicine.disease Xenograft Model Antitumor Assays In vitro Disease Models Animal 030104 developmental biology Pyrimidines Oncology Doxorubicin 030220 oncology & carcinogenesis Cancer research Signal Transduction |
| Zdroj: | Technology in cancer researchtreatment. 15(5) |
| ISSN: | 1533-0338 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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