拓扑替康对裸鼠非小细胞肺癌的治疗效果及机制研究  

Therapeutic effect and mechanism of topotecan on non-small cell lung cancer in nude mice

作　　者：任磊鹏 张新伟 王瑞洁 李潜 孙党泽 刘玉钢 REN Leipeng;ZHANG Xinwei;WANG Ruijie;LI Qian;SUN Dangze;LIU Yugang(Department of Thoracic Surgery,Xi'an Chest Hospital,Xi'an 710100,China)

机构地区：[1]西安市胸科医院胸外科,陕西西安710100 [2]陕西省肿瘤医院胸外科,陕西西安710065 [3]西安市东方医院内科,陕西西安710043

出　　处：《陕西医学杂志》2022年第6期676-679,701,共5页Shaanxi Medical Journal

基　　金：陕西省重点研发计划项目(2020SF-117)。

摘　　要：目的:探讨拓扑替康(TPT)对裸鼠非小细胞肺癌(NSCLC)的治疗效果及可能机制。方法:于每只裸鼠左侧腋部皮下注射0.2 ml H1993细胞悬浊液进行造模。将造模成功的裸鼠随机分成对照组(CG组)、TPT低剂量组(LG组)、TPT中剂量组(MG组)和TPT高剂量组(HG组),每组20只。TPT给药组以TPT灌胃,剂量依次为0.5、1.0、1.5 mg/(kg·d)。CG组裸鼠灌胃等量0.9%氯化钠溶液。每日1次,连续给药30 d。记录各组裸鼠的体重、死亡情况、肿瘤体积、瘤细胞凋亡率。检测裸鼠肿瘤组织中半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、Ki-67抗原(Ki-67)、血管内皮生长因子C(VEGFC)、基质金属蛋白酶-2(MMP-2)和胱抑素C的表达情况。结果:给药30 d时,LG组、MG组和HG组裸鼠体重明显高于CG组,死亡率明显低于CG组(均P<0.05)。与CG组比较,LG组、MG组和HG组裸鼠Ki-67、VEGFC、MMP-2、胱抑素C表达水平,以及肿瘤体积、细胞凋亡率显著降低,肿瘤抑制率和Caspase-3表达水平显著升高(均P<0.05)。结论:TPT可降低NSCLC移植瘤裸鼠的病死率,对NSCLC移植瘤具有较好的抑制作用,其机制可能与TPT增加H1993细胞Caspase-3蛋白表达,降低胱抑素C、Ki-67及MMP-2蛋白表达水平有关。Objective:To investigate the therapeutic effect of topotecan(TPT)on non-small cell lung cancer(NSCLC)in nude mice and its possible mechanism.Methods:The model was established by subcutaneous injection of 0.2 ml H1993 cell suspension into the left axillary of each nude mouse.After successful modeling,nude mice were randomly divided into control group(CG group),TPT low dose group(LG group),TPT medium dose group(MG group)and TPT high dose group(HG group),with 20 mice in each group.TPT administration group was given TPT by gavage at doses of 0.5,1.0 and 1.5 mg/(kg·d),nude mice in CG group were gavaged with equal amounts of 0.9%sodium chloride solution,once daily for 30 days.Body weight,death,tumor volume and apoptosis rate of tumor cells were recorded.The expression of Caspase-3,Ki-67,VEGFC,MMP-2 and cystatin C in tumor tissues of nude mice were detected.Results:After 30 days of administration,the weight of nude mice in LG,MG and HG groups was significantly higher than that in CG group,and the mortality rate was significantly lower than that in CG group(all P<0.05).Compared with CG group,the expression levels of Ki-67,VEGFC,MMP-2,cystatin C,as well as tumor volume and apoptosis rate of nude mice in LG,MG and HG groups were significantly decreased,while the tumor inhibition rate and Caspase-3 expression level were significantly increased(all P<0.05).Conclusion:TPT can reduce the mortality of nude mice with NSCLC xenograft and has a good inhibitory effect on NSCLC xenograft.The mechanism may be related to the increase of Caspase-3 protein expression and the decrease of cystatin C,Ki-67 and MMP-2 proteins expression in H1993 cells.

关 键 词：非小细胞肺癌 拓扑替康 裸鼠 半胱氨酸天冬氨酸蛋白酶-3 血管内皮生长因子C 基质金属蛋白酶-2 

分 类 号：R734.2[医药卫生—肿瘤]