MMP-2 siRNA inhibits radiation-enhanced invasiveness in glioma cells.
MMP-2 siRNA inhibits radiation-enhanced invasiveness in glioma cells.
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DOI：
10.1371/journal.pone.0020614
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Rao JS
中科院分区：
文献类型：
--
作者：
Badiga AV;Chetty C;Kesanakurti D;Are D;Gujrati M;Klopfenstein JD;Dinh DH;Rao JS
我们之前的工作和其他人的工作强烈表明胶质瘤的浸润表型与MMP-2的表达之间存在关系。放射治疗是胶质瘤治疗的主要手段之一，已知通过诱导MMP-2增加细胞侵袭。因此，抑制MMP-2为提高恶性胶质瘤放疗的疗效提供了一种潜在的手段。我们测试了质粒载体介导的MMP-2 siRNA （p-MMP-2）在人胶质瘤细胞系U251和U87中调节电离辐射诱导的侵袭表型的能力。与对照组和转染psv的细胞相比，转染p-MMP-2的细胞在有和没有辐射的情况下，MMP-2明显减少。与对照组相比，观察到转染p-MMP-2并结合辐射的细胞增殖、迁移、侵袭和血管生成显著减少。Western blot分析显示，辐射增强的VEGF、VEGFR-2、pVEGFR-2、p-FAK和p-p38水平被p- mmp -2转染的细胞抑制。TUNEL染色显示，辐射未诱导U87和U251细胞凋亡，但与对照组相比，辐射细胞同时转染p-MMP-2时，TUNEL阳性细胞明显增加。与对照组相比，单独使用p-MMP-2或联合放射治疗的动物颅内肿瘤生长明显受到抑制。由p-MMP-2介导并联合放疗的MMP-2抑制，通过调节几种重要的下游信号分子并引导细胞凋亡，显著减少肿瘤细胞的迁移、侵袭、血管生成和肿瘤生长。综上所述，我们的研究结果证明了p-MMP-2在抑制放射增强肿瘤侵袭和进展方面的有效性，并表明它可能作为胶质瘤患者放射治疗的有效辅助剂。
Our previous work and that of others strongly suggests a relationship between the infiltrative phenotype of gliomas and the expression of MMP-2. Radiation therapy, which represents one of the mainstays of glioma treatment, is known to increase cell invasion by inducing MMP-2. Thus, inhibition of MMP-2 provides a potential means for improving the efficacy of radiotherapy for malignant glioma. We have tested the ability of a plasmid vector-mediated MMP-2 siRNA (p-MMP-2) to modulate ionizing radiation-induced invasive phenotype in the human glioma cell lines U251 and U87. Cells that were transfected with p-MMP-2 with and without radiation showed a marked reduction of MMP-2 compared to controls and pSV-transfected cells. A significant reduction of proliferation, migration, invasion and angiogenesis of cells transfected with p-MMP-2 and in combination with radiation was observed compared to controls. Western blot analysis revealed that radiation-enhanced levels of VEGF, VEGFR-2, pVEGFR-2, p-FAK, and p-p38 were inhibited with p-MMP-2-transfected cells. TUNEL staining showed that radiation did not induce apoptosis in U87 and U251 cells while a significant increase in TUNEL-positive cells was observed when irradiated cells were simultaneously transfected with p-MMP-2 as compared to controls. Intracranial tumor growth was predominantly inhibited in the animals treated with p-MMP-2 alone or in combination with radiation compared to controls. MMP-2 inhibition, mediated by p-MMP-2 and in combination with radiation, significantly reduced tumor cell migration, invasion, angiogenesis and tumor growth by modulating several important downstream signaling molecules and directing cells towards apoptosis. Taken together, our results demonstrate the efficacy of p-MMP-2 in inhibiting radiation-enhanced tumor invasion and progression and suggest that it may act as a potent adjuvant for radiotherapy in glioma patients.
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DOI：
10.1016/s0360-3016(96)00244-1
发表时间：
1996-08-01
影响因子：
7
作者：
HaasKogan, DA;Yount, G;Israel, MA
通讯作者：
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DOI：
10.1152/ajplung.2001.280.1.l30
发表时间：
2001-01-01
影响因子：
4.9
作者：
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通讯作者：
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影响因子：
5.7
作者：
Engelhorn, Tobias;Savaskan, Nic E.;Eyuepoglu, Ilker Y.
通讯作者：
Eyuepoglu, Ilker Y.
影响因子：
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作者：
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