没食子酸联合顺铂通过下调环氧化酶-2抑制食管癌的实验研究  

Combination of gallic acid and cisplatin inhibits esophageal cancer by downregulating COX-2

作　　者：张仲卫[1] 李志刚[2] 李彩霞[3] ZHANG Zhong-wei;LI Zhi-gang;LI Cai-xia(Department of Thoracic Surgery,Tianjin Nankai Hospital,Tianjin(300100),China)

机构地区：[1]天津市南开医院胸外科,天津300100 [2]海南省肿瘤医院中西医结合科,海口570100 [3]天津市南开医院,中西医结合急腹症研究所,天津300100

出　　处：《中国中西医结合外科杂志》2024年第4期562-567,共6页Chinese Journal of Surgery of Integrated Traditional and Western Medicine

基　　金：天津市卫生健康委科技基金(2015KY27)。

摘　　要：目的:探究没食子酸(GA)和顺铂(DDP)是否能对食管癌细胞产生协同抗肿瘤作用。方法:将人食管癌细胞株KYSE150细胞接种于裸鼠左侧肋腹皮下,建立KYSE150细胞荷瘤裸鼠模型,待肿瘤生长至直径约5~7 mm时,将裸鼠随机分为对照组、GA组、DDP组及联合(GA+DDP)组。分别于干预后1、2、3、4周给各组裸鼠称重并测定各组肿瘤体积,计算肿瘤抑制率。干预后4周处死裸鼠,取肿瘤组织及血清。采用RT-qPCR、Western blot和ELISA法检测环氧化酶(COX)-2及其衍生物前列腺素E_(2)(PGE_(2))的表达水平。体外研究方面,分别用GA、DDP及联合组处理食管癌细胞系EC9706和KYSE150,用MTT实验检测细胞活力变化;用RT-qPCR、Western blot和ELISA法分别检测COX-2及PGE_(2)的表达。结果:与对照组相比,各给药组体重在喂养过程中都在增加,但无统计学差异。GA组、DDP组和联合组肿瘤体积均比对照组显著减小,且三组显著降低食管癌组织中COX-2 mRNA及COX-2蛋白的表达及血清中PGE_(2)的含量(P<0.05)。与GA和DDP单独使用相比,联合用药抑瘤效果更好(P<0.05)。GA组、DDP组和联合组均能显著降低食管癌细胞的增殖、COX-2 mRNA及COX-2蛋白表达以及PGE_(2)含量(P<0.05)。与GA和DDP单独使用相比,联合用药抑制作用更明显(P<0.05)。结论:GA联合DDP在体内、外均具有协同抗食管癌的活性,且可能成为一个非常有前景的食管癌临床治疗策略。Objective This study aimed to understand whether(Gallic acid,GA)and DDP could generate a synergistic antitumor effect on ESCC cells.Methods Human esophageal carcinoma cell KYSE150 cells were subcutaneously injected into the mice.When the tumor grew to about 5-7 mm in diameter,the nude mice were randomly divided into control group,GA group,DDP group and combined(GA+DDP)group.The body weight and tumor volume were measured once a week.Nude mice were sacrificed 4 weeks after injection,and the tumor tissues and serum were collected.The expression of COX-2 and its derivative PGE_(2) were detected by RT-qPCR,Western blot and ELISA.In vitro,esophageal cancer cell lines EC9706 and KYSE150 were treated with GA,DDP and the combined group for 24 h and 48 h.Cell viability were detected by MTT assay;The expression of COX-2 and PGE_(2) were detected by RT-qPCR,Western blot and ELISA.Results Compared with the control group,the body weight of each treatment group was increased during feeding,but there was no significantly difference.The tumor volume of GA group,DDP group and combined group were all significantly lower than that of control group,and the expression of COX-2 in esophageal cancer tissues and the content of PGE_(2) in serum were significantly decreased(P<0.05).Among these,the combination induced the most significant difference compared to the GA or DDP alone(P<0.05).In vitro,GA and DDP are demonstrated to restrain ESCC cell proliferation in a time-and dose-dependent mode.GA and DDP could significantly reduce the expression of COX-2 and the content of PGE_(2) in the supernatant(P<0.05).The inhibition was more pronounced in the combined group compared to the GA or DDP alone(P<0.05).Conclusion GA combined with DDP has synergistic activity against esophageal cancer in vitro and in vivo,and may become a very promising clinical treatment strategy for esophageal cancer.

关 键 词：没食子酸 顺铂 食管癌 环氧化酶-2 前列腺素E2 

分 类 号：R966[医药卫生—药理学]