塞来昔布对Lewis肺癌细胞的增殖抑制作用及其机制

J4 ›› 2010, Vol. 36 ›› Issue (1): 58-62.

塞来昔布对Lewis肺癌细胞的增殖抑制作用及其机制

徐志刚¹, 陈立¹, 吕晓艳¹, 李伟¹, 项丹¹, 李志军²

(1.吉林大学基础医学院药理学系,吉林长春 130021;2. 吉林大学第一医院胸外科,吉林长春 130021)

收稿日期:2009-10-14 出版日期:2010-01-28 发布日期:2010-01-28
通讯作者: 李志军 E-mail:（Tel：0431-85612973，E-mail：lizhijun@jlu.edu.cn）
作者简介:徐志刚（1974-）|男|吉林省长春市人|助理工程师|在读医学博士|主要从事肿瘤分子药理学研究。
基金资助:
吉林省科技厅科技发展计划项目资助课题（200705163）

Inhibitory effect of celecoxib on proliferation of Lewis lung cancer |cells and its mechanism

XU Zhi-Gang¹, CHEN Li¹, LU Xiao-Yan¹, LI Wei¹, XIANG Dan¹, LI Zhi-Jun²

(1. Department of Pharmacology,School of Basic Medical Sciences,Jilin University,Changchun 130021,China;2.Department of Thoracic Surgery,First Hospital,Jilin University,Changchun 130021,China)

Received:2009-10-14 Online:2010-01-28 Published:2010-01-28

摘要/Abstract

摘要：

目的：观察塞来昔布对Lewis肺癌细胞增殖及其移植瘤生长的抑制作用，并探讨其作用机制。方法：不同剂量（0、50、100和200 μmol•L^-1）塞来昔布与Lewis肺癌细胞共培养12、24、48和72 h，MTT比色法检测细胞增殖抑制率，RP-HPLC法检测24 h细胞培养上清液花生四稀酸含量，ELISA法检测24 h细胞培养上清液前列腺素E2含量。20只C57BL/6小鼠进行Lewis肺癌移植瘤实验，小鼠随机分为对照组和200 mg•kg^-1剂量给药组，于接种后3 d塞来昔布灌胃给药，连续用药15 d后处死小鼠，计算肿瘤的体积和质量。结果：50、100和200 μmol•L^-1塞来昔布均可抑制Lewis细胞增殖，其细胞增殖抑制率高于对照组(P< 0.05)；随着剂量和作用时间的增加，肿瘤细胞增殖抑制率增加，72 h的IC50值为（134.06±2.97） μmol•L^-1。与对照组比较，50 μmol•L^-1塞来昔布组培养上清液中花生四烯酸含量无变化，前列腺素E2含量降低（P<0.05），100和200 μmol•L^-1塞来昔布组，随着塞来昔布剂量的增加，培养上清液中花生四烯酸的含量增加（P<0.01），前列腺素E2的含量降低（P<0.01）。塞来昔布给药组小鼠的平均瘤质量均低于对照组（P<0.05），抑瘤率为50%。结论：塞来昔布可在体内及体外抑制Lewis肺癌细胞增殖，其机制可能是通过增加花生四烯酸及降低前列腺素E2水平发挥其抗肿瘤作用。

关键词: 塞来昔布；癌, Lewis肺；花生四烯酸；前列腺素E2

Abstract:

Abstract:Objective To investigate the inhibitory effects and possible anticarcinogenic mechanism of celecoxib on the proliferation of Lewis lung carcinoma cells in vitro and in vivo.Methods The proliferation of Lewis lung carcinoma cells　treated with different doses (50,100 and 200 μmol?L-1) of celecoxib for 12,24,48 and 72 h,was measured by MTT assay.The contents of arachidonic acid and prostaglandin E2 in the culture supernatants at 24 h were measured by the methods of RP-HPLC and PGE2-specific ELISA respectively.Twenty C57BL/6 mice receiving tumor implantation were divided randomly into control group and treatment(200 mg•kg^-1) groups. All the groups were gavaged continuously with normal saline or celecoxib on the third day after implantation.The mice were killed on the 15th day,and the volume and weight of the tumor tissues were calculated.Results Compared with control group,50,100 and 200 μmol•L^-1 celecoxib inhibited the proliferation of Lewis cells (P<0.05),the inhibitory rate was increased with the dose and time of treatment.The IC50 value of 72 h was (134.06±2.97) μmol•L^-1.Compared with control group,celecoxib had no effect on the arachidonic acid content,but depressed the prostaglandin E2 level in the culture supernatants in 50 μmol•L^-1 treatment group (P<0.05). In 100 and 200 μmol•L^-1　 treatment groups,celecoxib significantly increased the content of arachidonic acid and depressed the prostaglandin E2 level in the culture supernatants with the increasing of the dose of celecoxib (P<0.01). The solid tumor volume and weight in treatment group were lower than those in control group (P<0.05), and the tumor inhiitory rate in treatment group was 50%.Conclusion Celecoxib can inhibit the growth of Lewis lung carcinoma cells in vitro and in vivo.The anticarcinogenic effect of celecoxib depends on not only increasing the prodcution of arachidonic acid,but also inhibiting the synthesis of prostaglandin E2 in Lewis lung carcinoma treated with celecoxib.

Key words: celecoxib;carcinoma,lewis lung;arachidonic acid;prostaglandin E2

中图分类号:

R734.2

徐志刚, 陈立, 吕晓艳, 李伟, 项丹, 李志军. 塞来昔布对Lewis肺癌细胞的增殖抑制作用及其机制[J]. J4, 2010, 36(1): 58-62.

XU Zhi-Gang, CHEN Li, LU Xiao-Yan, LI Wei, XIANG Dan, LI Zhi-Jun. Inhibitory effect of celecoxib on proliferation of Lewis lung cancer |cells and its mechanism[J]. J4, 2010, 36(1): 58-62.

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