摘要
背景与目的:环氧化酶-2(cyclooxygenase-2,COX-2)与肺癌血管生成、淋巴转移相关,COX-2抑制剂能够抑制肺癌侵袭和转移。该研究探讨COX-2抑制剂艾瑞昔布能否抑制肺腺癌A549细胞裸鼠移植瘤侵袭和转移及其机制,以及与洛铂联合应用的疗效。方法:将肺腺癌A549细胞接种于30只BALB/c雄性裸鼠右侧腋部皮下,建立移植瘤模型。将造模成功裸鼠(n=29)随机分为4组:对照组(n=7)、艾瑞昔布组(n=8)、洛铂组(n=7)和艾瑞昔布联合洛铂组(n=7)。对照组灌胃等量灭菌蒸馏水及尾静脉注射等量0.9%Na Cl溶液,治疗组分别给予灌胃艾瑞昔布片每日40 mg/kg及尾静脉注射洛铂每周7.5 mg/kg相应处理。每日观察裸鼠饮食、活动等一般情况。给药6周后处死裸鼠,剥取移植瘤组织。应用免疫组织化学法和real-time PCR分别检测各组肿瘤PTEN、cortactin蛋白及相应m RNA表达水平。采用单因素方差分析及非参数检验进行统计学分析。结果:最后1周发现所有裸鼠饮食、活动较之前减少,逐渐消瘦,洛铂组及联合组变化较明显。与对照组相比,艾瑞昔布组及联合组PTEN蛋白及其m RNA表达明显升高,差异有统计学意义(P均<0.001);与对照组相比,艾瑞昔布组及联合组cortactin蛋白及其m RNA表达明显降低,差异有统计学意义(P均<0.001)。PTEN与cortactin蛋白、PTEN m RNA与cortactin m RNA均呈显著负相关(r=-0.660、-0.983,P均<0.001)。结论:艾瑞昔布能够抑制非小细胞肺癌侵袭和转移,其作用机制可能与上调PTEN蛋白及下调cortactin蛋白表达有关。艾瑞昔布对洛铂化疗可能具有增敏作用。
Background and purpose： Cyclooxygenase-2 （COX-2） participates in angiogenesis and lymph node metastasis of lung cancer. COX-2 inhibitors could inhibit invasion and metastasis of lung cancer. This study aimed to investigate the inhibition of invasion and metastasis by COX-2 inhibitor imrecoxib in xenograft tumor of lung adenocarcinoma A549 cell in nude mice and to explore its possible mechanisms, in addition, to observe the efficacy of imrecoxib combined with lobaplatin. Methods： Thirty male BALB/c nude mice were injected subcutaneously with A549 cells into the right axillary region to establish xenograft models. Twenty-nine successfully modeled mice were randomly divided into four groups： control group （n=7）, imrecoxib group （n=8）, lobaplatin group （n=7）, imrecoxib combined with lobaplatin group （n=7）. The control group was treated with the same amount of sterile distilled water and injected with the same amount of 0.9% sodium chloride solution via caudal vein. The treatment group was treated with imrecoxib tablets 40 mg/kg per day through gavage and injected with lobaplatin 7.5 mg/kg per week via caudal vein respectively. The diet, physical activity and other normal conditions of nude mice were observed everyday. After 6 weeks, 29 mice were sacrificed and transplanted tumor tissues were cut off. The expression of PTEN, cortactin protein and mRNA were detected by immunohistochemistry and real-time PCR. The data were analyzed with one-way anova and non-parametric test. Results： In the last week, the diet and physical activity of all nude mice were less than before, and they became thinner, which were more obvious among the mice in lobaplatin group and imrecoxib combined with lobaplatin group. Compared with the control group, the expression of PTEN protein and mRNA were significantly increased in imrecoxib group and imrecoxib combined with lobaplatin group （P〈0.001, respectively）. Compared with the control group, the expression of cortactin protein and mRNA were significantly decre
作者
王玲婵
崔立静
王东昌
赵云霞
赵志芳
陈刚
WANG Lingchan CUI Lijing WANG Dongchang ZHAO Yunxia ZHAO Zhifang CHEN Gang(Department of Respiratory Medicine, the Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei Province, China)
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2017年第1期1-6,共6页
China Oncology
基金
河北省省级重大医学科研课题(zd2013029)
