[Show abstract][Hide abstract] ABSTRACT: This study was aimed to further explore the apoptosis-inducing effect of bortezomib combined with cytarabine (Ara-C) on U937 cell line. Proliferation and apoptosis in U937 cells treated with bortezomib and/or Ara-C were assessed by cell count. Cell cycle distribution and reactive oxygen species (ROS) production level were measured by using flow cytometry. Cell signaling pathway related to apoptosis was analyzed by Western blot. The results showed that 10 nmol/L bortezomib combined with 50 nmol/L Ara-C significantly inhibited U937 cell proliferation. These two drug combination synergistically induced apoptosis in U937 cells, significantly increased cellular ROS level, and up-regulated the expression of phosphorylated form of JNK and P38 and down-regulated phosphorylation of ERK. It is concluded that the apoptosis of U937 cells synergistically induced by bortezomib combined with low concentration Ara-C is possibly associated with up-regulation of phosphorylated form of JNK, P38 and down-regulation of phosphorylation of ERK induced by increase of ROS, resulting in decrease of mitochrondrial potential.
No preview · Article · Nov 2012 · Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology
[Show abstract][Hide abstract] ABSTRACT: This study was aimed to explore the effect of bortezomib and low concentration cytarabine (Ara-C) on proliferation and apoptosis in U937 cell line and its mechanism. The proliferation and apoptosis of U937 cells treated with bortezomib (10 nmol/L) and(or) Ara-C (50 nmol/L) were observed by cell count, cell morphology, flow cytometry and Western blot. The results showed that bortezomib and Ara-C alone inhibited U937 cell proliferation. The inhibitory effect was enhanced by combination of these two drugs, the inhibitory rates of U937 cell proliferation were (55.00 ± 2.81)% and (70.02 ± 3.33)% after treatment for 24 h and 48 h, respectively. Bortezomib and Ara-C synergistically induced apoptosis and decreased mitochondrial membrane potential in U937 cells. The percentage of Rhodamin123 positive cells was (38.70 ± 1.54)%. Bortezomib and Ara-C also synergistically induced activation of caspase-9, caspase-8 and caspase-3. It is concluded that the bortezomib and low concentration Ara-C synergistically induced apoptosis in U937 cells, mainly through mitochondrial pathway, and possibly through death receptor pathway.
No preview · Article · Jun 2012 · Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology