[Synergistic effects of arsenic trioxide and proteasome inhibitor bortezomib on apoptosis induction in Raji cell line].
The aim of this study was to explore the synergistic effect of arsenic trioxide and bortezomib on apoptosis of Raji cell line. The cells were treated with arsenic trioxide, bortezomib, low-dose arsenic trioxide combined with bortezomib, respectively. The cell viability and proliferative curve were estimated by trypan blue dye exclusion. The cell apoptosis and cell cycle status were analyzed by flow cytometry. The apoptosis related elements such as caspase-3, BCL-2, BAX, JNK2 and IkappaB-alpha, were measured with Western blot. The results showed that compared with cells treated with mentioned above drugs alone, the proliferative potential of cells in combination group was significantly inhibited (p < 0.01), and apoptosis rate markedly increased (p = 0.001), while obvious cell cycle arrest was not observed. On the protein level, the expression of Caspase-3, BAX and IkappaB-alpha increased, while the expression of BCL-2, and JNK2 decreased. It is concluded that low-dose arsenic trioxide combined with bortezomib synergistically induced apoptosis in Raji cell line which may be mediated by inhibiting NK-kappaB and JNK2 signaling.
He
Yi
Y
Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
Yang
Jian-Min
JM
Wang
Jian-Min
JM
Zhou
Hong
H
Lü
Shu-Qing
SQ
Hu
Xiao-Xia
XX
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002051:Burkitt Lymphoma / Q000473:pathology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001152:Arsenicals; D001897:Boronic Acids; D010087:Oxides; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D000077237:Arsenic Trioxide