Bortezomib induces apoptosis in human neuroblastoma CHP126 cells.
Neuroblastoma (NB), the most frequent solid tumor of early childhood, is diagnosed as a disseminated disease in >60% of cases, and several lines of evidence support the resistance to apoptosis as a prerequisite for NB progression, and new treatment modalities or potent drugs are further needed. Bortezomib owns a substantial cytotoxicity through regulating degradation of protein associated with cell cycle control and tumor growth. The involvement of bortezomib in neuroblastoma is largely unkown. The aim of this study was to investigate the effects and mechanisms of bortezomib on human neuroblastoma CHP126 cells. Our results indicated that bortezomib inhibits proliferation of neuroblastoma cells in a time- and dose- dependent manner, and the concentration that caused 50% inhibition of CHP126 cells growth was 11.25 nM. Furthermore, bortezomib-induced proliferation inhibition results from massive cell death characterized by apoptosis. Besides, the NFkappaB pathway was not involved in bortezomib treatment in neuroblastoma CHP126 cells, bortezomib-driven apoptotic events were associated with promoting p21 and Bax expression and down-regulating Bcl-2 expression. Ultimately, caspase-3 was activated and the cleavage of PARP was induced. Above all, our data revealed that bortezomib triggered apoptosis by enhancing the caspase 3 activation and/or modulating the Bax/Bcl-2 balance, and also provided preliminary data for further researches of bortezomib on pediatric neuroblastoma.
Luo
Peihua
P
Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Lin
Meihua
M
Lin
Meili
M
Zhu
Difeng
D
Wang
Zhen
Z
Shen
Jingshan
J
Yang
Bo
B
He
Qiaojun
Q
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D016328:NF-kappa B / Q000096:biosynthesis; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D000970:Antineoplastic Agents; D001897:Boronic Acids; D004396:Coloring Agents; D007202:Indicators and Reagents; D016328:NF-kappa B; D011719:Pyrazines; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D000069286:Bortezomib; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D015689:Oncogene Protein p21(ras); C022616:thiazolyl blue