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目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮对人结肠癌LOVO细胞化疗敏感性的影响。方法体内实验:建立人结肠癌LOVO细胞裸鼠移植瘤模型,应用罗格列酮、5-Fu及两药联用连续灌胃给药两周,每2天测量瘤体的最长径和最短径,计算肿瘤体积和抑制率;体外实验:采用MTT法检测罗格列酮、5-Fu及两药联用对LOVO细胞生长的抑制作用,Hoechst染色检测细胞核形态,碘化丙啶(PI)染色流式细胞术检测细胞周期分布,Western blotting法检测Cyclin A1、Cyclin E1和Cdk2蛋白的表达变化。结果体内实验:罗格列酮、5-Fu及其联合用药组对裸鼠移植瘤抑制率分别为67.97%、74.9%和80.49%,两药联合为相加作用;体外实验:罗格列酮能够增强5-Fu对细胞的生长抑制作用,并呈现剂量和时间依赖性;细胞周期检测显示,5-Fu联合罗格列酮使S期细胞增多;与对照组相比,5-Fu处理组及联合用药组Cyclin A1表达量下调显著(P<0.01),与5-Fu组相比,联合用药组Cyclin A1表达量下调显著(P<0.01);与对照组相比,实验各用药组Cyclin E1、Cdk2表达量均下调显著(P<0.01),与5-Fu组相比,联合用药组Cyclin E1表达量下调显著。结论罗格列酮能够增强5-Fu的化疗效果,其机制与其诱导细胞凋亡及S期细胞周期阻滞有关。
Objective To investigate the effect of rosiglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, on the chemosensitivity of human colon carcinoma LOVO cells. Methods In vivo experiments: The human ovarian carcinoma model of LOVO cells was established. Rosiglitazone, 5-Fu and the two drugs were administered continuously for two weeks. The longest diameter and the shortest length of the tumor were measured every 2 days And calculate the tumor volume and inhibition rate. In vitro experiments: MTT assay was used to detect the inhibitory effect of rosiglitazone and 5-Fu on the proliferation of LOVO cells. Hoechst staining was used to detect the nuclear morphology, propidium iodide (PI) The cell cycle distribution was examined by flow cytometry. The expressions of Cyclin A1, Cyclin E1 and Cdk2 were detected by Western blotting. Results In vivo, the inhibitory rates of rosiglitazone, 5-Fu and their combination groups on the xenografts in nude mice were 67.97%, 74.9% and 80.49%, respectively. The in vitro experiments showed that rosiglitazone, 5- 5-Fu combined with rosiglitazone increased the number of S-phase cells. Compared with the control group, the 5-Fu treatment group (P <0.01). Compared with 5-Fu group, the expression of Cyclin A1 in combination group was significantly decreased (P <0.01). Compared with the control group, the expression of Cyclin A1 E1 and Cdk2 were down-regulated significantly (P <0.01). Compared with 5-Fu group, the expression of Cyclin E1 in combination group was significantly down-regulated. Conclusions Rosiglitazone can enhance the chemotherapeutic effect of 5-Fu, and its mechanism is related to its induction of apoptosis and S phase cell cycle arrest.