p27Kip1 的共转导强烈增强了 U-373MG 胶质瘤细胞中 Fas 配体和半胱天冬酶 8 介导的细胞凋亡。
Co-transduction of p27Kip1 strongly augments Fas ligand- and caspase-8-mediated apoptosis in U-373MG glioma cells.
作者信息
Shinoura N, Furitsu T, Asai A, Kirino T, Hamada H
机构信息
Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Cancer Institute, Tokyo, Japan.
出版信息
Anticancer Res. 2001 Sep-Oct;21(5):3261-8.
BACKGROUND
p27Kip1 is a potential tumor suppressor gene. As malignant gliomas express Fas at high levels, the relationship between Fas-mediated apoptosis and p27Kip1 expression may improve therapeutic approaches for treating gliomas.
MATERIALS AND METHODS
In this study, we transduced U-373MG glioma cells with the Fas ligand or caspase-8 genes using adenovirus vectors after transduction of the p27Kip1 gene to induce cell cycle arrest in U-373MG cells, and evaluated the degree of apoptosis.
RESULTS
The results demonstrate that expression of p27Kip1 enhanced Fas ligand- or caspase-8-mediated apoptosis in U-373MG cells. Expression of apoptosis-related genes such as Bax, Bcl-X(L), Bcl-2 or caspase-8 were reduced by p27Kip1 transduction compared with that of beta-actin, whereas p27Kip1 transduction did not affect the expression level of Fas or the Fas ligand.
CONCLUSION
Combined transduction of p27Kip1 with Fas ligand or caspase-8 would overide the resistance mechanism to apoptosis in malignant gliomas.
背景
p27Kip1是一种潜在的肿瘤抑制基因。由于恶性胶质瘤高水平表达Fas，Fas介导的细胞凋亡与p27Kip1表达之间的关系可能会改善胶质瘤的治疗方法。
材料与方法
在本研究中，我们在将p27Kip1基因转导至U-373MG细胞以诱导其细胞周期停滞之后，使用腺病毒载体将Fas配体或caspase-8基因转导至U-373MG胶质瘤细胞，并评估细胞凋亡程度。
结果
结果表明，p27Kip1的表达增强了U-373MG细胞中Fas配体或caspase-8介导的细胞凋亡。与β-肌动蛋白相比，p27Kip1转导使Bax、Bcl-X(L)、Bcl-2或caspase-8等凋亡相关基因的表达降低，而p27Kip1转导不影响Fas或Fas配体的表达水平。
结论
p27Kip1与Fas配体或caspase-8联合转导将克服恶性胶质瘤对细胞凋亡的抵抗机制。
Zotero 插件