title: Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Cuiyun
authors.initials: C
authors.lastname: Sun
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Hongxu
authors.initials: H
authors.lastname: Zhou
authors.forename: Shizhu
authors.initials: S
authors.lastname: Yu
authors.forename: Alain R
authors.initials: AR
authors.lastname: Simard
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.forename: Yanling
authors.initials: Y
authors.lastname: Kong
authors.forename: Tongling
authors.initials: T
authors.lastname: An
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wen
authors.forename: Fudong
authors.initials: F
authors.lastname: Shi
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D016372:RNA, Antisense / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D016372:RNA, Antisense; D020780:Matrix Metalloproteinase 9