相关信号通路阻断对子宫内膜癌裸鼠移植瘤生长影响  

EFFECTS OF BLOCKADE OF RELATED SIGNALING PATHWAYS ON THE GROWTH OF ENDOMETRIAL CARCINOMA XENOGRAFTS IN NUDE MICE

作　　者：朱博文 黄煜[2] 郑晶 颜莉莉[2] 林慧[2] 张清宇 ZHU Bowen;HUANG Yu;ZHENG Jing;YAN Lili;LIN Hui;ZHANG Qingyu(Qingdao University Medical Department, Qingdao 266034, China)

机构地区：[1]青岛大学医学部妇产学专业,山东青岛266034 [2]青岛大学附属青岛妇女儿童医院妇科中心

出　　处：《青岛大学学报（医学版）》2019年第4期442-446,共5页Journal of Qingdao University(Medical Sciences)

基　　金：山东省自然科学基金资助项目(ZR2013HM012)

摘　　要：目的探讨阻断趋化因子通路CXCL12/CXCR4、CXCR7及细胞外调节蛋白激酶(ERK)信号通路,对人子宫内膜癌Ishikawa细胞裸鼠皮下移植瘤的抑制作用。方法将子宫内膜癌Ishikawa细胞悬液与基质胶按1∶1混合,调整细胞密度为7.5×10^10/L,取200μL注射于裸鼠右侧背部肩胛皮下,制备子宫内膜癌动物模型,建模成功后随机分为AMD3100组、PD98059组、Anti-CXCR7组、AMD3100+Anti-CXCR7组和NaCl组(对照组),每组6只。各组裸鼠分别经腹腔给予相应药物,每3d给药1次,共3周。观察荷瘤裸鼠的状态及移植瘤的生长情况,绘制肿瘤生长曲线,计算抑瘤率;应用RT-PCR方法检测各组瘤体组织中凋亡抑制基因SurvivinmRNA的表达。结果治疗周期结束后,AMD3100组、PD98059组、Anti-CXCR7组、AMD3100+Anti-CXCR7组肿瘤体积及质量均低于对照组,抑瘤率明显高于对照组,瘤体组织SurvivinmRNA的表达低于对照组,差异有统计学意义(F=11.35~72.27,P<0.01);AMD3100组、PD98059组、Anti-CXCR7组、AMD3100+Anti-CXCR7组肿瘤体积、质量、抑瘤率及瘤体组织Survivinm RNA的表达比较差异均无显著性(P>0.05)。结论阻断CXCL12的特异性受体CXCR4、CXCR7以及细胞内ERK信号通路,能够抑制子宫内膜癌Ishikawa细胞裸鼠移植瘤的生长,其机制可能与瘤体组织凋亡抑制基因Survivin的下调有关。Objective To investigate the inhibitory effects of blocking the chemokine pathways CXCL12/CXCR4 and CXCR7 and extracellular regulated protein kinase (ERK) signaling pathway on subcutaneous xenografts of human endometrial carcinoma Ishikawa cells in nude mice. Methods Endometrial carcinoma Ishikawa cell suspension was mixed with Matrigel at a ratio of 1∶1, and the cell density was adjusted to 7.5×10^10 /L;200 μL of the mixture was subcutaneously injected into the right back scapula of nude mice to establish an animal model of endometrial carcinoma. After successful modeling, the animals were randomly divided into AMD3100 group, PD98059 group, anti-CXCR7 group, AMD3100+anti-CXCR7 group, and NaCl group (control group), with 6 animals in each group. Each group was administered intraperitoneally the corresponding drug, once every 3 d for 3 weeks. The status of tumor-bearing nude mice and the growth of transplanted tumor were observed. The tumor growth curve was plotted, and the tumor inhibition rate was calculated. The mRNA expression of apoptosis-inhibiting gene survivin in tumor tissues of each group was measured by RT-PCR. Results At the end of treatment cycle, the AMD3100 group, PD98059 group, anti-CXCR7 group, and AMD3100+anti-CXCR7 group had significantly lower tumor volume and weight, a significantly higher tumor inhibition rate, and significantly lower expression of Survivin mRNA in tumor tissues than the control group ( F =11.35- 72.27 , P <0.01). There was no significant difference in tumor volume and weight, tumor inhibition rate, and Survivin mRNA expression in tumor tissues between the AMD3100 group, the PD98059 group, the anti-CXR7 group, and the AMD3100+anti- CXCR7 group ( P >0.05). Conclusion Blocking CXCL12 specific receptors CXCR4 and CXCR7 and intracellular ERK signaling pathway can inhibit the growth of xenografts of endometrial carcinoma Ishikawa cells in nude mice, which may be related to the down-regulation of apoptosis-inhibiting gene Survivin in tumor tissues.

关 键 词：受体 CXCR4 趋化因子CXCL12 CXCR7 细胞外信号调节MAP激酶类 子宫内膜癌 

分 类 号：R737.33[医药卫生—肿瘤]