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Archive > Volume 26 Issue 8 > 2019,26(8):868-875. DOI:10.3872/j.issn.1007-385X.2019.08.007 Prev Next
Basic Research
Over-expression of programmed cell death 5 gene enhances chemosensitivity of brain glioma cells to temozolomide
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Abstract:
[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: A total 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 mRNA and 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 expres-sion 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 U251-siRNA group was significantly lower than that of the control group (both P<0.05). The tumor volume and weight of nude mice xenografts were compared, and the results showed control group>TMZ group>PDCD5 group>combined group (all P<0.05); however, the mRNAand 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 brain glioma to the chemotherapy drug TMZ, while silencing of PDCD5 expression exerts the opposite effect.Thecombination of PDCD5 and TMZ can better inhibit the growth of xenografts in nude mice.
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Project Supported:
Project supported by the "13th Five-Year" Science and Technology Project of Education Department of Jilin Province (No. JJKH20180332KJ)
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