蒿甲醚与顺铂联用对Lewis肺癌小鼠的抑瘤作用及其机制探讨  

The Inhibitory Effect and Mechanism of Artemether and Cisplatin on Lewise Lung Cancer Bearing C57BL/6J Mice

作　　者：万成亮[1] 蒋永新[1] 寸英丽[1] 金从国[1] 陈晓群[1] 李佳[1] 

机构地区：[1]昆明医学院第三附属医院云南省肿瘤医院,云南昆明650118

出　　处：《昆明医学院学报》2011年第3期21-26,44,共7页Journal of Kunming Medical College

基　　金：云南省科技厅基金资助项目(20082C145M);云南省教育厅基金资助项目(08C0122)

摘　　要：目的探讨蒿甲醚与顺铂联用对小鼠Lewis肺癌抑瘤效应及其作用机制.方法 C57BL/6J小鼠皮下接种3LL细胞(4×105/只)60只,随机分为六组,分别为1:生理盐水(NS)组;2:单用蒿甲醚(ARE)组;3:单用顺铂(DDP)组;4:先给蒿甲醚后给顺铂组;5:先给顺铂后给蒿甲醚组;6:蒿甲醚与顺铂同时给药组.观察各组小鼠的体重、瘤体积变化和抑瘤率,并评价两药联用的抑瘤作用.探讨蒿甲醚与顺铂联用时,不同给药顺序下抑瘤率的变化.瘤组织进行TUNEL和检测凋亡相关基因的表达.结果联合给药组肿瘤体积较生理盐水组瘤体积增长明显缓慢,而且明显慢于单用蒿甲醚或顺铂组;与生理盐水组比较,蒿甲醚组与顺铂组瘤体积增长速度较缓慢.蒿甲醚组与顺铂组抑瘤率分别为36.44%及50.29%,联合用药时(先用蒿甲醚组、先用顺铂组、同时用药组)抑瘤率分别为62.15%、65.54%、66.67%,与单用蒿甲醚或顺铂组比较有差异有统计学意义(P<0.05).在联合用药组之间抑瘤率差异无统计学意义(P>0.05).应用金氏公式评价蒿甲醚与顺铂联用对小鼠Lewis肺癌的抑制作用:联合给药时三种给药方式下其q值均:0.85<q<1.15,表明蒿甲醚与顺铂联用对小鼠Lewis肺癌有相加抑制作用.流式细胞术TUNEL检测结果显示,蒿甲醚与顺铂联用可通过诱导细胞凋亡来抑制Lewis肺癌小鼠瘤体积的生长.FCM法分析其对瘤组织凋亡相关基因检测表明蒿甲醚与顺铂联用能上调Fas、FasL、P53等凋亡基因,下调Bcl-2抑制凋亡基因.结论蒿甲醚与顺铂联用对小鼠Lewis肺癌有相加抑制作用,能促进肿瘤细胞凋亡,其机制可能与调控细胞凋亡相关基因的表达有关.Objective To study the anti-tumor effect and the mechanism of artemether and cisplatin on lung cancer bearing C57BL/6J mice.Methods C57BL/6J mice subcutaneously planted with 3LL lung cancer cell（4×105）were randomly divided into 6 groups;1：NS group;2：Artemether alone group;3：Cisplatin alone group;4：Artemether first and then use the cisplatin group;5：Cisplatin first and then use the artemether group;6： The same time give artemether and cisplatin group.The body weight changes and inhibitory rate of mice in each group were observed.And the inhibitory effect of the two drugs on tumor tissue was evaluated.The relationship between the order of combination therapy for the treatment and the inhibition rate was explored.In addition,the apoptosis of lung cancer cells and associated gene expression were analysed by TUNEL and flow cytometry.Results In the increase of tumor volume,the combined treatment group was significantly slower than the NS group,but also slower than use the drug artemether or cisplatin alone group.Compared with NS group,the tumor volume growth rate of artemether group or cisplatin group was slower.The tumor inhibition rates of artemether group and cisplatin group were 36.44% and 50.29%.The tumor inhibition rates of combined treatment（first give artemether group,first give cisplatin group,the same time give artemether and cisplatin group）were（62.15%,65.54%,66.67%）,compared with artemether alone group or cisplatin alone group（P0.05）.There was no difference in the tumor inhibition between the combined treatmentthe groups（P0.05）.Kim＇s formula was used to evaluate the synergy of combined treatment：the q values for the three modes of combined treatment were 0.85q1.15,that showed the additive inhibition of combined artemether and cisplatin in mice Lewis lung cancer.By flow cytometry,the result of TUNEL indicated that combined artemether and cisplatin can induce apoptosis and necrosis.Combined artemether and cisplatin group,the expression of apoptosis associated gene FasL/Fas

关 键 词：蒿甲醚 顺铂 LEWIS肺癌小鼠 抑制作用 

分 类 号：R734.2[医药卫生—肿瘤]