Over-expression of programmed cell death 5 gene enhances chemosensitivity of brain glioma cells to temozolomide
10.3872/j.issn.1007-385x.2019.08.007
- VernacularTitle:过表达程序性细胞死亡基因5提高脑神经胶质瘤细胞对替莫唑胺的化疗 敏感性
- Author:
WANG Lei
1
;
SHEN Weigao
2
;
LIU Yanbo
3
;
XU Haiyang
4
Author Information
1. Department of Neurosurgery,Affiliated Hospital of Beihua University
2. Department of Neurosurgery, Affiliated Hospital of Jilin Medical College
3. Department of Pathophysiology, School of Medicine
4. Department of Neurosurgery, First Clinical Hospital, Jilin University
- Publication Type:Journal Article
- Keywords:
programmed cell death 5 gene (PDCD5);
cerebral glioma;
U87 cell;
U251 cell;
temozolomide (TMZ);
chemosensitivity
- From:
Chinese Journal of Cancer Biotherapy
2019;26(8):868-875
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the role of tumor suppressor gene programmed cell death 5 gene (PDCD5) in the growth and temozolomide (TMZ) sensitivity of brain glioma cells. Methods:Atotal of 116 patients with cerebral glioma admitted to the Department of Neurosurgery, First Clinical Hospital of Jilin University from January 2009 to December 2014 were enrolled in this study. QPCR, WB and immunohistochemistry method were used to detect the mRNAand protein expressions of PDCD5 in glioma cell lines (U87, U251), U87 cell line with stable PDCD5 expression (U87-PDCD5), glioma cells with si-PDCD5 transfection and primary cerebral glioma tissues, respectively. MTT assay was used to detect the effect of over-expression or knockdown of PDCD5 on the growth and TMZ-sensitivity of glioma cells. The subcutaneous tumor-bearing model of glioma cell line U87 was established in nude mice, and then the experimental mice were randomly divided into control group, TMZ group, PDCD5 group and TMZ+exogenous PDCD5 recombinant expression vector group.After 20 days, the animals were sacrificed by cervical dislocation and the tumor tissue was excised to measure the tumor volume and weigh. The expression of PDCD5 in tumor tissues was detected by qPCR and WB methods, and the effects of PDCD5 combined with TMZ on the growth of gliomas were also analyzed. Results: The relative mRNA and protein expressions of PDCD5 in U87 cells were significantly lower than those in U251 cells (both P<0.05), and the mRNA and protein expressions of PDCD5 in high level glioma tissues were significantly lower than those in low level tissues (all P<0.05). The sensitivity of U87-PDCD5 cells and U251 cells to TMZ was higher than that of U87 cells (all P<0.05). The sensitivity of cells to TMZ in U87-PDCD5-siRNA group and U251siRNA group was significantly lower than that of the control group (both P<0.05). The tumor volume and weigh to fnudemicexenografts were compared,and the results showed control group>TMZ group>PDCD 5group>combined group(allP<0.05);however, the mRNA and protein expressions of PDCD5 in the transplanted tumor tissues of each group showed the opposite trend (all P<0.05). Conclusion: PDCD5 over-expression can enhance the chemosensitivity of braingliomato the chemotherapy drug TMZ, while silencing of PDCD5 expression exertsthe opposite effect.The combination of PDCD5 and TMZ can better inhibit the growth of xenografts in nude mice.
- Full text:20190807.pdf
