目的:研究TRAIL對卵巢癌COC1/DDP細胞生長的影響，以及化療藥物DDP等對TRAIL受體（DR4、DR5）表達的影響，揭示TRAIL與COC1/DDP細胞順鉑耐藥性的關系。方法:用MTT法檢測不同濃度TRAIL蛋白和TRAIL與DDP聯合用藥對COC1/DDP細胞生長的影響，用RTPCR方法檢測DDP對TRAIL受體（DR4、DR5）表達的影響。結果:①TRAIL蛋白對COC1/DDP細胞生長有抑制作用，且隨著TRAIL蛋白濃度升高，細胞抑制率逐漸上升。②DDP（2.5μg/mL）對COC1/DDP細胞生長抑制作用較弱（抑制率為3.31%），DDP在加入TRAIL蛋白后對細胞生長抑制率顯著升高（Plt;0.05）。③DDP使COC1/DDP細胞的DR5表達水平顯著增強為正常對照組的3.54倍（Plt;0.001）。結論:TRAIL蛋白對COC1/DDP細胞生長有抑制作用，DDP與TRAIL聯合使用COC1/DDP細胞生長抑制更明顯，TRAIL可逆轉COC1/DDP細胞對DDP的耐藥性，耐藥性的逆轉可能與DDP導致TRAIL受體DR5水平增高促進了腫瘤細胞的凋亡有關。
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 研究腫瘤壞死因子相關凋亡誘導配體（TRAIL）蛋白對SKOV3移植瘤細胞半胱天冬氨酸蛋白酶-3（Caspase-3）表達的影響及其與腫瘤細胞凋亡的關系。 方法 建立雌性裸小鼠SKOV3移植瘤24只，隨機分為4組，每組6只。TRAIL組單用重組人TRAIL蛋白（10 μg/kg），順鉑（DDP）組單用DDP（3 mg/kg），TRAIL+DDP組聯合使用TRAIL蛋白（10 μg/kg）和DDP（3 mg/kg），空白對照組給予0.5 mL生理鹽水。經處理后，各組的組織切片用免疫組織化學染色檢測Caspase-3的表達和末端脫氧核苷酸轉移酶介導核苷酸缺口標記技術（TUNEL）檢測腫瘤細胞凋亡指數。 結果 Caspase-3的表達水平在TRAIL組（171.67±14.38）、DDP組（172.50±14.75）、聯合組（230.00±40.99）中均明顯高于對照組（135.83±16.25）（Plt;0.05）。SKOV3移植瘤細胞凋亡指數在空白對照組、TRAIL組、DDP組和聯合組分別為16.67±5.43、33.17±8.42、24.33±4.59和40.50±6.16，TRAIL組和聯合組細胞凋亡指數較空白對照組和DDP組明顯增高（Plt;0.05）。 結論 TRAIL蛋白使卵巢癌移植瘤細胞的Caspase-3表達增強，TRAIL蛋白促進腫瘤細胞凋亡發生。【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.