摘要
目的:探究甲磺酸阿帕替尼对裸鼠食管癌的抗肿瘤作用,并分析可能的机制。方法:建立食管癌NEC细胞裸鼠皮下移植瘤模型40只,随机分为荷瘤组、实验A组、实验B组及5-氟尿嘧啶(5-Fu)组,每组10只。其中,实验A、B组分别给予8.3、16.6 mg/kg甲磺酸阿帕替尼灌胃处理,连续4周;荷瘤组同时间给予等量0.9%氯化钠溶液灌胃;5-Fu组腹腔注射130 mg/kg 5-Fu溶液。统计各组瘤体质量并计算肿瘤抑制率。采用原位末端转移酶标记(TUNEL)法检测各组肿瘤组织中细胞凋亡情况。采用实时荧光定量PCR(RT-qPCR)和免疫印迹法检测瘤体组织血管内皮生长因子受体2(VEGFR2)、p-VEGFR2、信号转导和转录激活因子3(STAT3)、p-STAT3、半胱天冬氨酸蛋白酶-3(Caspase-3)mRNA及蛋白表达水平。结果:荷瘤组、实验A组、实验B组及5-Fu组成瘤率为100%,模型均构建成功。分组后处理第12天时,实验A组、实验B组及5-Fu组裸鼠瘤体体积小于荷瘤组(均P<0.05)。随处理时间延长,实验B组及5-Fu组各时间点裸鼠瘤体体积小于实验A组(均P<0.05)。与荷瘤组比较,实验A组、实验B组及5-Fu组移植瘤瘤体质量减少,p-VEGFR2/VEGFR2、p-STAT3/STAT3蛋白表达降低,抑瘤率、细胞凋亡率、Caspase-3 mRNA及蛋白表达升高(均P<0.05),且实验B组、5-Fu组瘤体质量及p-VEGFR2/VEGFR2、p-STAT3/STAT3蛋白表达低于实验A组,抑瘤率、细胞凋亡率、Caspase-3蛋白表达高于实验A组(均P<0.05)。结论:甲磺酸阿帕替尼可抑制裸鼠食管癌移植瘤生长并促进细胞凋亡,其机制可能与抑制VEGFR2/STAT3通路有关。
Objective:To investigate the antitumor effect of apatinib mesylate on esophageal cancer in nude mice and to analyze the possible mechanism.Methods:Forty subcutaneous transplanted tumor models of esophageal cancer NEC cells in nude mice were successfully established and randomly divided into tumor bearing group,experimental group A,experimental group B and 5-Fu group,with 10 nude mice in each group.Experimental groups A and B were given 8.3 and 16.6 mg/kg apatinib mesylate by intragastric administration respectively,for 4 weeks.The tumor bearing group was given 0.9%sodium chloride solution at the same time.The 5-Fu group was intraperitoneally injected with 130 mg/kg 5-Fu solution.The tumor weight and the tumor inhibition rate of each group were calculated.The apoptosis of tumor cells in each group was detected by TUNEL assay.The mRNA and protein expressions of VEGFR2,p-VEGFR2,STAT3,p-STAT3 and Caspase-3 were detected by RT-qPCR and Western blot.Results:The tumor rate of tumor bearing group,experimental group A,experimental group B and 5-Fu was 100%,and the model was successfully constructed.On the 12th day of post-treatment,the tumor volume of nude mice in experimental groups A,B and 5-Fu was lower than that in tumor bearing group(all P<0.05).With the extension of treatment time,the tumor volume of nude mice in experimental group B and 5-Fu groups was smaller than that in experimental group A at each time point(all P<0.05).Compared with the tumor bearing group,tumor weight and protein expression of p-VEGFR2/VEGFR2 and p-STAT3/STAT3 were decreased,and tumor inhibition rate,cell apoptosis rate,Caspase-3 mRNA and protein in experimental groups A,B and 5-Fu were increased,and tumor weight and p-VEGFR2/VEGFR2 and p-STAT3/STAT3 protein expression in experimental groups B and 5-Fu were lower than those in experimental group A,while tumor inhibition rate,cell apoptosis rate and Caspase-3 protein expression were higher than those in experimental group A(all P<0.05).Conclusion Apatinib mesylate can inhibit the growth and promote apoptosis of transplanted tumor in nude mice with esophageal cancer,and the mechanism may be related to the inhibition of VEGFR2/STAT3 pathway.
作者
周敏
张艳霞
郭楠
田梅
ZHOU Min;ZHANG Yanxia;GUO Nan;TIAN Mei(Xinjiang Uiger Municipal People’s Hospital,Urumqi 830001,China)
出处
《陕西医学杂志》
CAS
2023年第12期1670-1674,共5页
Shaanxi Medical Journal
关键词
食管癌
裸鼠
甲磺酸阿帕替尼
血管内皮生长因子受体2
信号转导和转录激活因子3
Esophageal cancer
Nude mice
Apatinib mesylate
Vascular endothelial growth factor receptor 2
Signal transducer and activator of transcription 3
作者简介
通讯作者:田梅,E-mail:564820565@qq.com。
