ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of bortezomib in inducing apoptosis in imatinib-resistant K562 (K562R) cells and its possible mechanism.</p><p><b>METHODS</b>K562 cells were cultured in gradient concentrations of imatinib for several months to generate imatinib-resistant K562 cells. The viability of K562R cells treated with bortezomib was measured using CCK-8 cell proliferation assay, and the cell apoptosis was analyzed by flow cytometry with annexin V/PI dual staining. Western blotting was used to detect the protein expressions of Mcl-1,Bcl-2 and Bcr/Abl.</p><p><b>RESULTS</b>K562R cell line was successfully established, which showed 31.8 folds of imatinib resistance compared with the na?ve cells. Bortezomib treatment produced dose- and time-dependent inhibitory effect on the proliferation of both K562 cells and K562R cells and dose-dependently induced apoptosis in K562R cells. Combination of bortezomib with imatinib significantly enhanced the apoptosis of the cells. Western blotting showed that bortezomib treatment dose-dependently decreased the protein levels of both Mcl-1and Bcr/Abl in K562R cells without affecting bcl-2 protein expression.</p><p><b>CONCLUSION</b>Bortezomib can inhibit the proliferation of K562R cells and induce cell apoptosis possibly by down-regulating Mcl-1 and Bcr/Abl expression and enhancing Mcl-1 cleavage.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To study the effect and acting mechanism of puerarin preconditioning (PP) on blood level of cytokines in patients undergoing cardiopulmonary bypass (CPB) in perioperative period.</p><p><b>METHODS</b>Forty patients with heart diseases scheduled to take surgical operation were randomized into the control group and the PP group equally. They were treated with the same program, excepting that 0.6 g of puerarin was given to the PP group by adding in 5% glucose solution 250 mL for intravenous dripping every day for one week before operation, but to the control group, normal saline was given instead. The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6, 8 and 10 (IL-6, IL-8, IL-10) in arterial blood were measured at 5 time points in the process of CPB, namely, anesthetic induction (T1), 10 min after the clamp of the ascending aorta (T2), 10 min, 2 h and 12 h after the Clamped aorta is unclamped (T3, T4 and T5).</p><p><b>RESULTS</b>All the above-mentioned indexes (TNF-alpha, IL-6, IL-8 and IL-10) gradually increased after beginning CPB, reached the peak at T4, then lowered gradually but still presented the higher levels at T5 than those at T1 (P < 0.05). Comparison between the two groups showed that levels of TNF-alpha, IL-6 and IL-8 were significantly lower (P < 0.05 or P < 0.01) and level of IL-10 was higher in the PP group than those in the control group respectively at all the time points (P < 0.01).</p><p><b>CONCLUSION</b>Injecting puerarin before CPB could effectively suppress the pro-inflammatory cytokines like TNF-alpha, IL-6 and IL-8; and enhance the expression of anti-inflammatory cytokines like IL-10, thus to alleviate the inflammatory reaction induced by CPB.</p>