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2.
Chinese Journal of Hematology ; (12): 737-740, 2008.
Article in Chinese | WPRIM | ID: wpr-239965

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>


Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Antineoplastic Agents , Pharmacology , Apoptosis , Arsenicals , Pharmacology , Boronic Acids , Pharmacology , Bortezomib , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Multiple , Drug Resistance, Neoplasm , HL-60 Cells , Harringtonines , Pharmacology , Oxides , Pharmacology , Pyrazines , Pharmacology
3.
Journal of Southern Medical University ; (12): 1504-1506, 2007.
Article in Chinese | WPRIM | ID: wpr-283097

ABSTRACT

<p><b>OBJECTIVE</b>To assess the antitumor efficacy and adverse effects of bortezomib either used alone or in combination with arsenic trioxide for transplanted tumor in nude mice.</p><p><b>METHODS</b>Nude mice bearing HL-60 cell xenografts were randomized into 4 groups to receive treatment with normal saline, bortezomib, arsenic trioxide, bortezomib plus arsenic trioxide. The tumor growth inhibition and general condition of the nude mice were observed, and in situ TUNEL assay and immunohistochemistry were performed on the transplanted tumors.</p><p><b>RESULTS</b>Bortezomib alone and in combination with arsenic trioxide could both inhibit the growth of the transplanted tumors, prolong the survival of the nude mice, and induce cell apoptosis and growth inhibition of the HL-60 cells in vivo, and the combined administration exhibited even better effects. The administration was well tolerated with causing manifest vital organ damages in the mice.</p><p><b>CONCLUSION</b>Bortezomib in combination with arsenic trioxide has significant antitumor effect in nude mice bearing HL-60 cell xenografts possibly by inducing HL-60 cell apoptosis and growth inhibition without producing no significant adverse effects.</p>


Subject(s)
Animals , Humans , Male , Mice , Apoptosis , Arsenicals , Pharmacology , Boronic Acids , Pharmacology , Bortezomib , Cell Proliferation , Disease Models, Animal , HL-60 Cells , Leukemia , Drug Therapy , Mice, Nude , Oxides , Pharmacology , Pyrazines , Pharmacology , Random Allocation , Xenograft Model Antitumor Assays
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