[Apoptosis in Jurkat cells induced by bortezomib combined with adriamycin].
OBJECTIVE
The aim of this study was to observe the suppressive effect of bortezomib alone and the synergistic suppressive effect of bortezomib and adriamycin on the proliferation of the cell line Jurkat cells, and to discuss the mechanism of apoptosis induced by bortezomib.


METHODS
The suppressive effect of bortezomib and adriamycin on the proliferation of Jurkat cells in vitro was detected by MTT colorimetry, and the morphology of the cells was examined by histology. The cell apoptosis was measured by flow cytometry with Annexin V/PI staining and cell cycle analysis. The effect of bortezomib and adriamycin on the expression levels of caspase-3, caspase-8 and PARP were measured by Nestern blot.


RESULTS
The proliferation of Jurkat cells was significantly inhibited by bortezomib treatment (between 10 - 320 ng/ml) for 24 h, 48 h and 72 h, and the growing inhibition ratio showed a positive correlation with the drug concentration (r(24 h) = 0.900, P < 0.01; r(48 h) = 0.849, P < 0.01; r(72 h) = 0.679, P < 0.01), in a concentration-dependent manner. The IC(50) of Jurkat cells treated with bortezomib in a dose of 10 - 320 ng/ml was 137.64 +/- 6.82 ng/ml, but the IC(50) of Jurkat cells treated with bortezomib combined with adriamycin (125 ng/ml) for 24 h was significantly decreased to 20.44 +/- 2.85 ng/ml. The apoptosis rate had a positive correlation with the concentration of bortezomib (P < 0.01). After the Jurkat cells were treated with bortezomib, apparent shear bands of caspase-8, caspase-3 and PARP proteins were observed.


CONCLUSIONS
There is an effect of Bortezomib to induce apoptosis in Jurkat cells, and the extrinsic pathway is one of the apoptosis-inducing mechanisms. There is a synergistic suppressive effect of the combination of bortezomib and adriamycin on the proliferation of Jurkat cells and enhances their chemosensitivity.
Chen
Jun-fa
JF
Department of Hematology, Zhejiang University of Traditional Chinese Medicine, Hangzhou 310006, China.
Jin
Jie
J
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000069286:Bortezomib; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8