目的:研究TRAIL对卵巢癌COC1/DDP细胞生长的影响,以及化疗药物DDP等对TRAIL受体(DR4、DR5)表达的影响,揭示TRAIL与COC1/DDP细胞顺铂耐药性的关系。方法:用MTT法检测不同浓度TRAIL蛋白和TRAIL与DDP联合用药对COC1/DDP细胞生长的影响,用RTPCR方法检测DDP对TRAIL受体(DR4、DR5)表达的影响。结果:①TRAIL蛋白对COC1/DDP细胞生长有抑制作用,且随着TRAIL蛋白浓度升高,细胞抑制率逐渐上升。②DDP(2.5μg/mL)对COC1/DDP细胞生长抑制作用较弱(抑制率为3.31%),DDP在加入TRAIL蛋白后对细胞生长抑制率显著升高(Plt;0.05)。③DDP使COC1/DDP细胞的DR5表达水平显著增强为正常对照组的3.54倍(Plt;0.001)。结论:TRAIL蛋白对COC1/DDP细胞生长有抑制作用,DDP与TRAIL联合使用COC1/DDP细胞生长抑制更明显,TRAIL可逆转COC1/DDP细胞对DDP的耐药性,耐药性的逆转可能与DDP导致TRAIL受体DR5水平增高促进了肿瘤细胞的凋亡有关。
Objective To evaluate the relationship between COPD and atherosclerosis, and analyze the risk factors of atherosclerosis among COPD patients. Methods A total of 40 COPD patients and 43 normal subjects were enrolled in the study. Carotid intima-media thickness (IMT) and plaques were detected in both groups. Blood samples were collected to measure the concentration of high sensitive C-reactive protein (hs-CRP) , fibrinogen (Fbg) , total cholesterol (TC) , triglyceride (TG) , high density lipoprotein cholesterol (HDL-C) , low density lipoprotein cholesterol (LDL-C) , while smoking index was recorded. Multiple regression analysis was performed to evaluate the correlative factors of IMT among COPD patients. According to whether luminal stenosis appeared, the COPD patients were allocated into group A ( without luminal stenosis) and group B ( with luminal stenosis) . Age, gender, hs-CRP, Fbg, TC, TG, HDL-C, LDL-C, and smoking index of the two groups were compared respectively. Results Hs-CRP, Fbg, thickness of IMT, plaques detection rate, and smoking index in the COPD group were significantly higher than those in the control group ( Plt;0.05) . TC, HDL-C, LDL-C in the COPD group were significantly lower than those in the control group ( Plt;0. 05) .Multiple regression analysis of IMT correlative factors among COPD patients showed that age, hs-CRP, Fbg, TC, TG, LDL-C, HDL-C, and smoking index were in linear relationship with IMT thickening. Age, hs-CRP, TC, and smoking index were positively correlated with IMT ( Plt;0.05) . Hs-CRP and smoking index in the group A were lower than those in the group B ( Plt;0. 05) .While TC, TG, LDL-C, and HDL-C in the group A were higher than those in the group B ( Plt;0.05) . Conclusions Age, smoking index, hs-CRP, and TC are risk factors for thickening of carotid artery IMT in COPD patients. Furthermore, smoking index, hs-CRP, TC, TG, LDL-C, and HDL-C are related to the severity of IMT thickening. The ultrasound detection of carotid artery IMT can be a valuble tool to screen atherosclerosis in patients with COPD.
【摘要】 目的 研究肿瘤坏死因子相关凋亡诱导配体(TRAIL)蛋白对SKOV3移植瘤细胞半胱天冬氨酸蛋白酶-3(Caspase-3)表达的影响及其与肿瘤细胞凋亡的关系。 方法 建立雌性裸小鼠SKOV3移植瘤24只,随机分为4组,每组6只。TRAIL组单用重组人TRAIL蛋白(10 μg/kg),顺铂(DDP)组单用DDP(3 mg/kg),TRAIL+DDP组联合使用TRAIL蛋白(10 μg/kg)和DDP(3 mg/kg),空白对照组给予0.5 mL生理盐水。经处理后,各组的组织切片用免疫组织化学染色检测Caspase-3的表达和末端脱氧核苷酸转移酶介导核苷酸缺口标记技术(TUNEL)检测肿瘤细胞凋亡指数。 结果 Caspase-3的表达水平在TRAIL组(171.67±14.38)、DDP组(172.50±14.75)、联合组(230.00±40.99)中均明显高于对照组(135.83±16.25)(Plt;0.05)。SKOV3移植瘤细胞凋亡指数在空白对照组、TRAIL组、DDP组和联合组分别为16.67±5.43、33.17±8.42、24.33±4.59和40.50±6.16,TRAIL组和联合组细胞凋亡指数较空白对照组和DDP组明显增高(Plt;0.05)。 结论 TRAIL蛋白使卵巢癌移植瘤细胞的Caspase-3表达增强,TRAIL蛋白促进肿瘤细胞凋亡发生。【Abstract】 Objective To investigate the effects of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the expression of Cysteine/aspartic acid specific protease- 3 (Caspase-3) in SKOV3 ovarian tumor cells and its relationship with the apoptosis of the ovarian tumor xenografts in nude mice. Methods Twenty-four nude mice with SKOV3 cell line ovarian tumor were randomly divided into four groups with 6 in each group. TRAIL (10 μg/kg) was given to the mice in the TRAIL group; DDP (3 μg/kg) was given to the mice in the DDP group; TRAIL (10 μg/kg) and DDP (3 μg/kg) were given to the mice in the TRAIL+DDP group; and 0.5 mL of saline solution was give to the mice in the control group. The expression of Caspase-3 was detected with immunohistochemistry. The apoptosis index (AI) of cells was determined by Terminal deoxynucleotidyl transferase mediated-dUTP nick end labeling (TUNEL). Results The expression of Caspase-3 in the TRAIL group (171.67±14.38), DDP group (172.50±14.75), and TRAIL+DDP group (230.00±40.99) was significantly higher than that in the control group (135.83±16.25) (Plt;0.05). The apoptosis index for the control group, TRAIL group, DDP group and TRAIL+DDP group was 16.67±5.43, 33.17±8.42, 24.33±4.59, and 40.50±6.16, respectively. The apoptosis index for the TRAIL group and the TRAIL+DDP group was significantly higher than that in the control group and the DDP group (Plt;0.05). Conclusion Soluble TRAIL has an effect on enhancing the expression of Caspase-3 in implanted tumor in nude mice. TRAIL protein can inhibit the growth of SKOV3 cells in nude mice by inducing cell apoptosis.
Objective To investigate the expressions of tumor necrosis factor related apoptosis inducing ligand (TRAIL) and its receptors (DR4, DcR1) in human rectal cancer tissues and normal rectal tissues. MethodsThe expressions of TRAIL and its receptors (DR4, DcR1) in 31 cases of human rectal cancer tissues and 20 cases of normal rectal tissues were detected by immunohistochemical staining. ResultsThe positive expression rates of TRAIL, DR4 and DcR1 (32.26%, 29.03%, 0) were lower than those of normal rectal tissues (55.00%, 70.00%, 65.00%), the difference was statistically significant(P=0.015, P=0.000, P=0.000). There were no relation between the expressions of TRAIL, DR4 and DcR1 and clinicopathologic characteristics (Pgt;0.05). ConclusionThe expressions of TRAIL and its receptors (DR4, DcR1) in human rectal cancer tissues were lower than those of normal rectal tissues, which may suggest that the apoptotic effect induced by the interaction between TRAIL and its receptors has attenuated in human rectal cancer.