RESUMEN
OBJECTIVE: To assess effects of proteasome inhibitor Bortezomib (Bor) in combination with Daunorubicin (DNR) on proliferation, apoptosis and the expression of Bcl-2 mRNA in primary leukemia cells in vitro. METHODS: Primary leukemia cells were isolated from bone marrow of adult acute leukemia patients using Ficoll liquid, then the primary leukemia cells were treated with different concentration of these two drugs (Bor 5, 10, 20, 50 nmol/L, DNR 50, 100, 200, 500 nmol/L, and Bor 5, 10 nmol/L combined with DNR 50, 100, 200, 500 nmol/L respectively ). Cells proliferation, IC50 and CDI were analyzed by MTT assay, cellular apoptosis was observed by flow cytometry, Bcl-2 mRNA was analyzed by RT-PCR. RESULTS: Growth inhibition ratio of all the types of acute leukemia cells were increased with the treatment of DNR and Bor in dose-dependent manner. Combined with Bor (5, 10 nmol/L),the IC50 of DNR decreased from (102 +/- 27) nmol/L to (73 +/- 26), (55 +/- 22) nmol/L respectively. DNR 200 nmol/L combined with Bor 10 nmol/L showed a better synergism (CDI = 0. 17). Compared with control group and single drug (DNR or Bor) group, there were obvious increase of apoptosis ratio and obvious decrease of Bcl-2 in the group of DNR 100 nmol/L combined with Bor 20 nmol/L after 24 h or 48 h cultivation (P < 0.05). CONCLUSION: Bor combined with DNR shows synergetic effect in promoting the apoptosis of adult acute leukemia primary cells as well as inhibitory effect on the proliferation of leukemia cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Ácidos Borónicos/farmacología , Daunorrubicina/farmacología , Leucemia Mieloide Aguda/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pirazinas/farmacología , Adulto , Antibióticos Antineoplásicos/farmacología , Antineoplásicos/farmacología , Bortezomib , Sinergismo Farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células Tumorales Cultivadas , Adulto JovenRESUMEN
OBJECTIVE: To study the proliferative inhibition effects of imatinib, daunorubicin and bortezomib on two leukemia cell lines with Ph(+), chronic myelogenous leukemia cell line K562 expressing P210 protein and acute lymphoblastic leukemia cell line SUP-B15 expressing P190 protein. METHODS: (1) The cells of the two cell lines treated with imatinib, daunorubicin and bortezomib for 72 hours were analyzed by MTT assay for proliferation. The proliferative activity was displayed by growth curve and IC50 value. (2) The bcr-abl transcriptant in the cells treated with imatinib (final concentration at 0, 0.35, 1 micromol/L) for 48 hours was detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) The IC50 values of K562 and SUP-B15 cell lines treated with imatinib, daunorubicin and bortezomib for 72 hours were respectively (0.286 +/- 0.060) micromol/L, (0.303 +/- 0.009) micromol/L, (22.127 +/- 3.592) nmol/L and (1.387 +/- 0.180) micromol/L, (0.117 +/- 0.017) micromol/L, (12.350 +/- 0.740) nmol/L. (2) There was no change of bcr-abl expression level in both cell lines after the treatment of imatinib. CONCLUSION: Imatinib, daunorubicin and bortezomib showed anti-cancer effects on Ph(+) leukemia cells in vitro. K562 cells were more sensitive to imatinib than the other two drugs, whereas SUP-B15 cells are more sensitive to daunorubicin and bortezomib. The short time intervention of imatinib has no effect on the expression of bcr-abl in Ph (+) leukemia cell lines.