期刊
NEUROSCIENCE BULLETIN
卷 29, 期 1, 页码 83-93出版社
SPRINGER
DOI: 10.1007/s12264-012-1296-5
关键词
matrix-degrading metalloproteinase 9; antisense MMP-9 RNA; cell proliferation; malignant glioma cells
资金
- National Natural Science Foundation of China [30770827, 31170864, 81100887]
- National Basic Research Development Program of China (973 Program) [2010CB529405]
- Key Laboratory Project of Tianjin Municipality for Science and Technology [10SYSYJC28800]
- Major Program of Research on Applied Fundamentals and Frontier Technologies [10JCZDJC19400]
- Key Program of Higher Education of Tianjin Municipality for Science and Technology [2004ZD06, 20060202]
- Program for New Century Excellent Talents in University of China [NCET-11-1067]
- Key Project of Natural Science Foundation of Tianjin Municipality, China [12JCZDJC24200]
- Key Project for Science and Technology of Ministry of Education, China [212005]
The matrix-degrading metalloproteinases (MMPs), particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA (pcDNA-ASMMP9), which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4- to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex (AS-MMP-9-treated group), subcutaneous injection of endostatin (endostatin-treated group), or both (combined therapy group). Mice treated with pcDNA (empty vector)-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.
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