非甾体类消炎药对卵巢癌抑制作用的研究

发布时间：2018-10-12 11:53

【摘要】：目的研究不同类型的非甾体类消炎药对卵巢癌细胞是否有等同于顺铂或较之更强烈的抑制作用,以选择更有可能应用于临床的新型药物。方法选取64只BALB/c-nu/nu裸鼠,8周龄,体质量(20±2)g,采用DISS细胞建立腹水型卵巢癌裸鼠模型和OVCAR-3细胞建立体表固体瘤裸鼠模型。研究2种非甾体类消炎药,即1种非选择性环氧化酶(cyclooxygenase,COX)抑制剂(阿司匹林)和1种选择性COX-2抑制剂(美洛昔康),对癌性腹水裸鼠生存期限、固体肿瘤的生长以及对裸鼠体内前列腺素E2(prostaglandin E2,PGE2)水平、血管内皮生长因子(vascalar endothelial growth factor,VEGF)表达的影响,并与顺铂的作用效果比较。采用随机数字表法分为对照组、顺铂组、阿司匹林组和美洛昔康组。结果在恶性腹水模型中对照组平均生存时间为(32.8±1.7)d,顺铂组为(53.9±4.1)d,阿司匹林组为(35.4±2.0)d,美洛昔康组为(56.5±4.9)d。实验第7天,对照组裸鼠体表转移瘤体积为(1.70±0.67)cm3,顺铂组为(0.51±0.18)cm3,阿司匹林组为(0.77±0.21)cm3,美洛昔康组为(0.72±0.38)cm3,差异有统计学意义,F=13.205,P0.001。恶性腹水模型中对照组PGE2浓度为(679.53±203.54)pg/mL,顺铂组为(405.69±142.41)pg/mL,阿司匹林组为(154.94±48.52)pg/mL,美洛昔康组为(167.85±59.74)pg/mL,差异有统计学意义,F=29.206,P0.001。在转移瘤实验中,对照组裸鼠血清中PGE2浓度为(647.49±62.22)pg/mL,顺铂组为(435.33±38.67)pg/mL,阿司匹林组为(196.28±35.15)pg/mL,美洛昔康组为(158.61±42.30)pg/mL,差异有统计学意义,F=195.465,P0.001。对照组VEGF浓度为(533.44±82.07)pg/mL,顺铂组为(376.54±37.84)pg/mL,阿司匹林组为(452.44±42.27)pg/mL,美洛昔康组为(263.62±41.52)pg/mL,差异有统计学意义,F=36.252,P0.001。结论在体内试验中,不同类型的非甾体类消炎药对卵巢癌肿瘤细胞抑制作用不同,选择性COX-2抑制剂美洛昔康的作用较强,近似于一线抗卵巢癌药物-顺铂,选择性COX-2抑制剂在卵巢癌临床治疗中的应用值得进行更广泛的研究。
[Abstract]:Objective to study whether different types of nonsteroidal anti-inflammatory drugs (NSAIDs) have the same or stronger inhibitory effects on ovarian cancer cells as cisplatin in order to select new drugs that are more likely to be used in clinic. Methods Sixty-four BALB/c-nu/nu nude mice, 8 weeks old, with body weight of (20 卤2) g, were used to establish ascites ovarian carcinoma nude mice model and OVCAR-3 cells to establish solid tumor model. Two kinds of non-steroidal anti-inflammatory drugs, one non-selective cyclooxygenase (cyclooxygenase,COX) inhibitor (aspirin) and one selective COX-2 inhibitor (meloxicam), were studied for the survival of nude mice with cancerous ascites. The growth of solid tumor and its effect on the expression of prostaglandin E 2 (prostaglandin E 2) and vascular endothelial growth factor (vascalar endothelial growth factor,VEGF) in nude mice were compared with those of cisplatin. The patients were randomly divided into control group, cisplatin group, aspirin group and meloxicam group. Results in the malignant ascites model, the mean survival time was (32.8 卤1.7) days in the control group, (53.9 卤4.1) days in the cisplatin group, (35.4 卤2.0) days in the aspirin group and (56.5 卤4.9) days in the meloxicam group. On the 7th day, the volume of metastatic tumor in nude mice was (1.70 卤0.67) cm3, (0.51 卤0.18) cm3, aspirin, (0.77 卤0.21) cm3, meloxicam, and (0.72 卤0.38) cm3, respectively. In the malignant ascites model, the concentration of PGE2 in the control group was (679.53 卤203.54) pg/mL, (405.69 卤142.41) pg/mL, in the aspirin group, (154.94 卤48.52) pg/mL, in the meloxicam group and (167.85 卤59.74) pg/mL, in the control group, and the difference was statistically significant in the control group (679.53 卤203.54) pg/mL, cisplatin group and (154.94 卤48.52) pg/mL, meloxicam group (P 0.001). In metastatic tumor test, the serum PGE2 concentration of nude mice in the control group was (647.49 卤62.22) pg/mL, (435.33 卤38.67) pg/mL, aspirin group was (196.28 卤35.15) pg/mL, meloxicam group and (158.61 卤42.30) pg/mL, level in the control group was (158.61 卤42.30) pg/mL, while that in the control group was (647.49 卤62.22) pg/mL, (435.33 卤38.67) pg/mL, aspirin group, and (158.61 卤42.30) pg/mL, in the control group. The concentration of VEGF in control group (533.44 卤82.07) pg/mL, cisplatin group was (376.54 卤37.84) pg/mL, aspirin group was (452.44 卤42.27) pg/mL, meloxicam group and pg/mL, was (263.62 卤41.52) pg/mL,. Conclusion in vivo, different types of non-steroidal anti-inflammatory drugs have different inhibitory effects on ovarian cancer cells, and the selective COX-2 inhibitor meloxicam has a strong effect, which is similar to cisplatin, a first-line anti-ovarian cancer drug. The application of selective COX-2 inhibitors in the clinical treatment of ovarian cancer deserves more extensive study.
【作者单位】：中国医科大学附属盛京医院妇产科;
【分类号】：R737.31

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