摘要
探讨酪氨酸蛋白激酶抑制剂(TKI)联合放疗治疗乳腺癌荷瘤小鼠的实验效果及作用机制。取MCF-7细胞皮下注射建模成功的乳腺癌荷瘤小鼠模型48只,采用随机数字表法分为对照组(等量生理盐水灌胃)、TKI组(舒尼替0.25 mg/次,2 d/次)、放疗组(X线照射治疗)、联合组(舒尼替0.25 mg/次,2 d/次联合X线照射治疗)各12只,对比两组肿瘤体积、抑瘤率,采用RT-PCR技术检测肿瘤组织中表皮生长因子(EGFR)m RNA、AKT1 m RNA、Cyclin D1 m RNA的水平、采用ELISA法检测各组小鼠血清中金属蛋白酶组织抑制剂(TIMP-1)、酪氨酸激酶受体A(Trk A)、酪氨酸激酶受体B(Trk B)的浓度。在连续给药20 d,TKI组、放疗组、联合组小鼠的肿瘤瘤体体积显著小于对照组(p<0.05);联合组的肿瘤瘤体体积显著小于TKI组和放疗组(p<0.05),联合组的抑瘤率显著高于TKI组、放疗组(p<0.05);TKI组、放疗组、联合组小鼠的肿瘤组织EGFR m RNA、AKT1 m RNA、Cyclin D1 m RNA的水平显著低于对照组(p<0.05);联合组的肿瘤组织EGFR m RNA、AKT1 m RNA、Cyclin D1 m RNA的水平显著低于TKI组和放疗组(p<0.05);TKI组、放疗组、联合组小鼠血清TIMP-1、Trk A、Trk B水平显著的低于对照组(p<0.05);联合组的血清TIMP-1、Trk A、Trk B水平显著低于TKI组和放疗组(p<0.05)。TKI联合放疗治疗乳腺癌荷瘤小鼠效果显著优于单纯TKI或放射治疗。
The aim of this study was to investigate the effect and mechanism of tyrosine protein kinase inhibitor(TKI) combined with radiotherapy on the treatment of breast cancer bearing mice. 48 breast cancerbearing mice successfully modeled by MCF-7 cells subcutaneous injection were selected and divided into control group(normal saline), TKI group(sunitinib 0.25 mg/time, 2 day 1 time), radiotherapy group(X-ray irradiation treatment), and combined group(sunitinib 0.25 mg/time, 2 day 1 time combined with X-ray irradiation). According to the random number method, with 12 mice in each group. Tumor volume and tumor inhibition rate of the two groups were compared. RT-PCR technology was applied to detect the level of m RNA, AKT1 m RNA and Cyclin D1 m RNA in EGFR of tumor. ELISA method was used to detect the concentration of TIMP-1, Trk A and Trk B in the serum of mice. After continuous administration of 20 d, the tumor volume of TKI group, radiotherapy group and combined group was signifi cantly smaller than the control group( p 〈0.05). Also, the tumor volume of combined group was smaller than that of TKI group and radiotherapy group(p〈0.05), and the anti-tumor rate of combined group was higher than that of TKI group and radiotherapy group( p〈0.05). The level of m RNA, AKT1 m RNA and Cyclin D1 m RNA in EGFR of tumor in TKI group, radiotherapy group and combined group was significantly lower than the control group(p〈0.05). In addition, the serum TIMP-1, Trk A and Trk B level in TKI group, radiotherapy group and combined group was significantly lower than the control group(p〈0.05). The serum TIMP-1, Trk A and Trk B level in combined group was significantly lower than that in TKI group and radiotherapy group( p〈0.05).Therefore, TKI combined with radiotherapy had better efficacy than pure TKI or radiotherapytherapy in the treatment of breast cancer bearing mice.
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2017年第12期5033-5039,共7页
Genomics and Applied Biology
基金
达州职业技术学院附属医院资助
关键词
酪氨酸蛋白激酶抑制剂
放疗
乳腺癌
荷瘤小鼠
Tyrosine protein kinase inhibitors
Radiotherapy
Breast cancer
Tumor bearing mice