现代妇产科进展2017，Vol.26Issue(3)：169-173,178,6.DOI:10.13283/j.cnki.xdfckjz.2017.03.002
生物钟基因Period2对裸鼠卵巢癌移植瘤生长和血管生成抑制作用的机制研究
Mechanism of biological clock gene Period2 on the growth and angiogenesis of ovarian cancer xenografts in nude mice
摘要
Abstract
Objective:To investigate the effects of circadian gene Period2 on the growth and angiogenesis of ovarian cancer xenografts in nude mice. Methods:Using ovarian cancer cell to construct ovarian cancer xenografts in nude mice,the exogenous gene Period2 was introduced into the recombinant gene by gene transfer technique,which was successfully expressed in tumor tissue. Real-time quantitative PCR and Western blot were used to detect the expression of Peri-od2 in xenografts tumors. The volume of xenografts tumors were measured during the treatment period,and after two weeks of treatment,the mice were sacrificed and the weight of the xeno-grafts tumors were measured. The expression of vascular endothelial growth factor/vascular per-meability factor VEGF/VPF,vascular endothelial growth factor receptor1 ( VEGFR1 ) and mi-crovessel density MVD ( CD34 marks) in tumor tissue were detected by immunohistochemistry. The expression of tumor metastasis associated gene MTA1,matrix metalloproteinase MMP-9,and PI3K/Akt signaling pathway was detected by western-blot method. Results:(1) Successful ex-pression of exogenous Period2 gene in transplanted tumor in nude mice. (2)Compared with the other two groups,the tumor volume of Period2 group was statistically significant (F=23. 469,P<0. 001). 2 weeks after transfection,transplanted tumor weight of Period2 group was significant-ly lower than the empty plasmid group and the control group,the difference was statistically sig-nificant (P<0. 05),and the tumor inhibition rate of Period2 reached 38. 9%. (3)Immunohisto-chemical results showed that VEGF/VPF,VEGFR1 expression decreased (F=46. 80/48. 09,P<0 . 001 ) , and MVD counts ( CD34 markers ) were significantly reduced ( F=138 . 4 , P<0. 001) in the Period2 group. (4)The results of Western blot showed that,MTA1 and MMP-9 of Period2 group were significantly less than that of the other groups (P<0. 05),and the protein expression of autophagy related signaling pathway PI3 K/Akt was significantly reduced ( P<0.05),compared with the other two groups,the difference was statistically significant (P<0. 001). Conclusion:(1)Exogenous Period2 overexpression could slow the growth rate of ovari-an cancer,and the tumor inhibition rate was significantly increased. (2)Period2 may inhibit the angiogenesis and invasion of ovarian cancer by inhibiting the expression of VEGF/VPF,MTA-1 and MMP-9 . ( 3 ) Period2 may interfere with PI3 K/Akt signaling pathway to inhibit autophagy and inhibit tumor blood vessels,so as to play a role in inhibiting tumor.关键词
卵巢癌/生物钟基因Period2/血管生成/肿瘤转移Key words
Ovarian carcinoma/Biological clock gene Period2/Angiogenesis/Tumor metastasis分类
医药卫生引用本文复制引用
李翠丽,王朝霞,李莉,李风艳..生物钟基因Period2对裸鼠卵巢癌移植瘤生长和血管生成抑制作用的机制研究[J].现代妇产科进展,2017,26(3):169-173,178,6.基金项目
山西省卫生计生委科研课题(No:2015024) （No:2015024）
