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Objective To study the enhancement of sensitivity to cisplatin (DDP) mediated by the addition of proteasome inhibitor Oprozomib (OZ) in ovarian cancer cells. Methods SKOV3/DDP and A2780/DDP cells were cultured in vitro, and the logarithmic growth phase cells were used in this study. To study the effect of OZ on drug-resistant cell viability, a series dilutions of OZ (0, 3, 9, 27, 81, 243, 729, 2181, and 6561 nmol/L) was used. The effect of DDP was also investigated with a series titrations (0, 3, 9, 27, 81, 243, 729, 2181 and 6561 nmol/L) in the presence of 50 μl of 500 nmol/L OZ. CCK-8 method was used to detect cell viability; flow cytometry was used to detect the apoptosis rate after treated with DDP+OZ. The experiments were divided into the control group and OZ group to detect the effects of OZ on the activity of proteasome chymotrypsin (CT-L), the synthesis of intracellular glutathione (GSH); the expression of intracellular glutathione synthetase (GSS) was examined using western blotting. The experiments were divided into the control group, DDP group, OZ group, DDP+OZ group, DDP+OZ+GSH group and DDP+OZ+Tempol group to detect the ROS level and apoptosis rate. Results The IC50 of OZ to SKOV3/DDP and A2780/ DDP cells were 140 and 350 nmol/L, respectively; In the presence of OZ, the IC50 of DDP to SKOV3/DDP and A2780/DDP cells were 154 and 232 nmol/L, respectively. The apoptosis rate of ovarian cancer cells increased significantly (P<0.01) after treated with DDP+OZ together. OZ can inhibit the CT-L activity of the proteasome in a dose-dependent manner and can inhibit GSH synthesis and GSS protein expression (P<0.01). The decrease of GSH level leads to the obstruction of ROS clearance, and the ROS level was significantly reduced by the ROS scavenger Tempol (P<0.05, P<0.01). Tempol significantly inhibits the apoptosis induced by DDP+OZ (P<0.01). Conclusion OZ enhanced sensitivity of SKOV3/DDP and A2780/DDP to cis-platinum by inhibiting the generation of GHS which resulted in the accumulation of ROS.
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AIM:To investigate the protective effect of zacopride (ZAC) on the pressure-overload left ventricular remodeling in the rats induced by coarctation of abdominal aorta.METHODS:Male Sprague-Dawley (SD) rats with pressure overload were induced by the coarctation of abdominal aorta.The model rats were intraperitoneally administered with ZAC, chloroquine (Chlor) , and zacopride+chlorquine (ZAC+Chlor).The study duration was 8 weeks.The cardiac structure and function were assessed by echocardiography.The heart weight/body weight (HW/BW) ratio and the left ventricular weight/body weight (LVW/BW) ratio were calculated.The changes of structure and shape in myocardial tissue were observed with HE staining.The ultrastructure of the myocytes was observed under transmission electron microscope.The inward rectifier potassium channel (IK1) protein expression was determined by Western blot.The mRNA expression of Kir2.1 was detected by RT-PCR.RESULTS:Compared with vehicle group, ZAC improved cardiac function, as indicated by the decreased left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic dimension (LVESD) (P<0.05) , and the increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01).The HW/BW and LVW/BW ratios were significantly decreased, and the cross-sectional area of the cardiomyocytes was significantly less in ZAC group than that in vehicle group (P<0.01).The ultrastructure of the myocytes was significantly improved.Chlor blocked the protective effect of zacopride on the pressure-overload left ventricular remodeling.The protein level ofmRNA expression of Kir2.1 in the cardiac tissues in ZAC group were significantly increased compared with vehicle group (P<0.01).CONCLUSION:ZAC significantly attenuates pressure overload-induced ventricular remodeling in rats.
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· AlM: To investigate the correlation of retinal vein occlusion ( RVO ) with blood lipids and carotid artery changes. · METHODS: Forty cases ( 40 eyes ) with RVO who presented to Eye Hospital of Xinxiang Medical University between May 2013 and April 2014 were selected as the research objects. Proceeded blood lipids and color doppler ultrasonography examination, including total cholesterol ( TC ) , triglycerides ( TG ) , high -density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol ( LDL-C ) , common carotid artery intima-media thickness, carotid plaques, internal carotid artery blood flow mechanics parameters were detected.Thirty eyes ( 30 cases ) were enrolled as control underwent above examinations. ·RESULTS:TC, TG, LDL-C of RVO group was obviously higher than those of the control group ( P0.05 ) . There were also no statistical difference between ipsilateral and contralateral carotid artery measured value of control group (P>0.05).There were no differences in age, sex between RVO group and control group (P>0.05). · CONCLUSlON: Lipid metabolism disorder, carotid artery changes is closely related to the pathogenesis of RVO.