[In vitro effect of bortezomib alone or in combination with harringtonine or arsenic trioxide on proliferation and apoptosis of multidrug resistant leukemia cells].
OBJECTIVE
To investigate the effect of bortezomib alone or combined with harringtonine (HT) or arsenic trioxide (As2O3) on the proliferation capacity and apoptosis of HL-60/ADM cell line and fresh cells from refractory/relapse acute leukemia patients.


METHODS
HL-60/ADM cells or refractory/relapse leukemia cells were incubated with bortezomib at different doses alone and in combination with HT or As2O3. The proliferation capacity was observed by MTT assay, cell apoptosis by fluorescence microscopy and flow cytometry. Intracellular concentration of daunorubicin (DNR) was determined by flow cytometry.


RESULTS
In bortezomib-treated HL-60/ADM cells, the proliferation inhibition rate and apoptotic cells increased in a time- and dose-dependent manner. 40 nmol/L bortezomib could maximally inhibit the proliferation of HL-60/ADM cells at 48 hours. 15 micromol/L As2O3 or 752 nmol/L HT combined with different doses of bortezomib could inhibit proliferation and induce apoptosis of HL-60/ADM cells. The As2O3 plus bortezomib or HT plus bortezomib showed a greater anticancer efficacy than either of the drugs alone (P < 0.05, P < 0.01). Bortezomib (10 nmol/L) could markedly enhance the intracellular accumulation of DNR in HL-60/ADM cells (P < 0.05).


CONCLUSIONS
Bortezomib can inhibit proliferation and induce apoptosis of HL-60/ADM cells and fresh refractory/relapse acute leukemia cells, especially combined with HT or As2O3.
Cai
Yan-xia
YX
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Meng
Fan-yi
FY
Sun
Qi-xin
QX
Fu
Yun-bi
YB
Li
Li
L
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D018922:HL-60 Cells; D006248:Harringtonines / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010087:Oxides / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D055815:Young Adult
D000970:Antineoplastic Agents; D001152:Arsenicals; D001897:Boronic Acids; D006248:Harringtonines; D010087:Oxides; D011719:Pyrazines; C062500:harringtonin; D000069286:Bortezomib; D000077237:Arsenic Trioxide