Bortezomib inhibits cell proliferation in prostate cancer.

Despite the improvement in chemotherapeutic agents, the outcome of patients with prostate cancer remains poor. It is therefore imperative that new anticancer drugs are explored. The aim of the present study was to investigate the inhibitory effect of bortezomib on DU145 prostate cancer cells. The DU145 cell proliferation rate was detected via MTT assay prior to and following exposure to various concentrations of bortezomib, and the level of cell apoptosis and the cell cycle distribution were tested using flow cytometry. In addition, western blotting was used to measure the expression of Bcl-2-interacting killer (Bik) and active-caspase-3. The results showed that bortezomib inhibited the proliferation of DU145 cells in a time- and dose-dependent manner. Following treatment with 1.6 µmol/l bortezomib, the DU145 cells showed marked nuclear condensation, chromatin condensation and fragmentation. Analysis of the cell cycle revealed a significantly increased percentage of cells in the G0/G1 phase and a decreased percentage in the S and G2/M phases. The rate of DU145 cell apoptosis was significantly higher in the bortezomib group than that in the control group, and this was accompanied by an enhanced expression of Bik and active-caspase-3. It can be concluded that bortezomib inhibits the proliferation of DU145 cells by inducing apoptosis. The underlying mechanism may involve the upregulation of Bik and active-caspase-3 expression.

Renovascular morphological changes in a rabbit model of hydronephrosis.

Obstructive nephropathy ultimately leads to end-stage renal failure. Renovascular lesions are involved in various nephropathies, and most renal diseases have an ischemic component that underlies the resulting renal fibrosis. The aim of this study was to investigate whether morphological changes occur in the renal vasculature in hydronephrosis and the possible mechanisms involved. A model of complete unilateral ureteral obstruction (CUUO) was used. Experimental animals were divided into five groups: a normal control group (N) and groups of animals at 1st week (O1), 2nd week (O2), 4th week (O4) and 8th week (O8) after CUUO. Blood pressure was measured, renal arterial trees and glomeruli were assessed quantitatively, and renovascular three-dimensional reconstruction was performed on all groups. Glomerular ultrastructural changes were examined by transmission electron microscopy. The results showed that the systolic blood pressure was significantly increased in the obstructed groups (O1, O2, O4 and O8). Three-dimensional reconstruction showed sparse arterial trees in the O8 group, and a tortuous and sometimes ruptured glomerular basement membrane was found in the O4 and O8 groups. Furthermore, epithelial media thickness and media/lumen ratio were increased, lumen diameters were decreased, and the cross-sectional area of the media was unaltered in the segmental renal artery, interlobar artery and afferent arterioles, respectively. In conclusion, renal arterial trees and glomeruli were dramatically altered following CUUO and the changes may be partially ascribed to vascular remodeling. Elucidation of the molecular mechanisms of renovascular morphological alterations will enable the development of potential therapeutic approaches for hydronephrosis.

Lefty A protein inhibits TGF-ß1-mediated apoptosis in human renal tubular epithelial cells.

This study aimed to examine the effects of Lefty A protein on transforming growth factor-ß1 (TGF-ß1)-mediated apoptosis in human renal tubular epithelial cells (HK-2). HK-2 cells were transfected with the human Lefty gene to induce the secretion of endogenous Lefty A protein. Following exposure of the HK-2 cells to recombinant human TGF-ß1 (10 ng/ml), p-Smad2/3 protein levels were examined by western blot analysis, and cellular apoptosis was detected by flow cytometry 6, 12, 24 and 48 h following TGF-ß1 treatment. Coculture of renal tubular epithelial cells with TGF-ß1 resulted in a significant increase in p-Smad2/3 protein levels and the rate of cell apoptosis, which were attenuated by liposome-mediated transfection with the Lefty gene. Lefty A protein was able to inhibit the TGF-ß1/Smad signaling pathway and markedly attenuate TGF-ß1-mediated apoptosis in human renal tubular epithelial cells. Taken together, these results indicated that the TGF-ß1/Smad signaling pathway most likely mediates apoptosis in renal tubular epithelial cells. In addition, Lefty A protein is capable of inhibiting the TGF-ß1/Smad pathway to reduce TGF-ß1/Smad-mediated apoptosis in renal tubular epithelial cells. This study may provide novel insights into the prevention and treatment of urinary tract obstruction disease using Lefty A protein.