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  • Title: [Effects of bortezomib combined with daunorubicin on proliferation and apoptosis in primary adult acute leukemia].
    Author: Zhou RQ, Gong YP, Zheng BH, Yang X.
    Journal: Sichuan Da Xue Xue Bao Yi Xue Ban; 2010 Sep; 41(5):789-92. PubMed ID: 21302442.
    Abstract:
    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.
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