非甾体类消炎药对卵巢癌抑制作用的研究  

Antitumor effect of NSAIDs on ovarian cancer

作　　者：辛兵[1] 吉凯强[1] 

机构地区：[1]中国医科大学附属盛京医院妇产科,辽宁沈阳110004

出　　处：《中华肿瘤防治杂志》2015年第16期1266-1269,1291,共5页Chinese Journal of Cancer Prevention and Treatment

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,P<0.001。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,P<0.001。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,P<0.001。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,P<0.001。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,OBJECTIVE To investigate whether the antitumor effects of non-steroidal anti-inflammatory drugs （NSAIDs） were better, at least, equaled to cisplatin（DDP）, a platinum-type anticaneer drug, on growth of epithelial o- varian caneer（EOC）. METHODS Tumor growth, survival, the levels of prostaglandin E2 （PGE2） and vascular endothe- lial growth factor（VEGF） were examined in female nu/nu mice xenografted with subcutaneous OVCAR-3 ceils or with in- traperitoneal DISS cells treated with two kinds of NSAIDs, one was non-selective COX inhibitor aspirin, the other was selective COX-2 inihitor meloxicam, and compared with DDP. RESULTS The survival time in cancerous peritonitis mice was （32.8±1.7） d in control group, （53. 9±4.1） d in DDP group, （35.4±2.0） d in aspirin group and （56.5 ±4.9） d inmeloxicam group. The tumor volumes were （1.70±0.67） cm3, （0.51±0.18） cm3, （0.77±0.21） cm3 and （0.72± 0.38） cm3. The difference was statistically significant （F= 13. 205, P〈0. 001）. The concentration of PGE2 in cancerous peritonitis mice ascites was （679. 3 ± 203. 54） pg/mL, （405. 69 ± 142. 41） pg/mL, （154. 94 ± 48. 52） pg/mL and （167. 854±59.74） pg/mL for the control, CDDP, aspirin and meloxicam groups, respectively. The difference was statis- tically significant （F=29. 206, P〈0. 001）. The concentrations of PGE2 in cancer-bearing mice serum were （647.49 ±62.22） pg/mL, （435.33±38.67） pg/mL, （196.28±35.15） pg/mL and （158. 61±42.30） pg/mL for the control, CD- DP, aspirin and meloxicam groups, respectively. The difference was statistically significant（F= 195. 465, P〈0. 001）. The concentrations of VEGF in cancerous peritonitis mice ascites were （533. 44±82.07） pg/mL, （376.54±37.84） pg/mL, （452. 44 ± 42. 27） pg/mL and （263. 62±41. 52） pg/mL, respectively. The difference was statistically significant （F=36. 252, P〈0. 001）. CONCLUSIONS NSAIDs have different antitumor affection on EOC in vivo. The antitumor

关 键 词：非甾体类消炎药 选择性环氧化酶-2抑制剂 顺铂 上皮性卵巢癌 

分 类 号：R737.31[医药卫生—肿瘤]