Intracavitary liposome-mediated p53 gene transfer into glioblastoma with endogenous wild-type p53 in vivo results in tumor suppression and long-term survival.
Intracavitary liposome-mediated p53 gene transfer into glioblastoma with endogenous wild-type p53 in vivo results in tumor suppression and long-term survival.
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腔内脂质体介导的 p53 基因转移到体内具有内源性野生型 p53 的胶质母细胞瘤中，可抑制肿瘤并实现长期存活。
DOI：
10.1006/bbrc.1997.6459
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Silverberg,GD
中科院分区：
文献类型：
--
作者：
Hsiao,M;Tse,V;Carmel,J;Tsai,Y;Felgner,PL;Haas,M;Silverberg,GD
通过将表达内源性野生型p53的RT-2细胞注射到裸小鼠腹腔中来建立空腔胶质母细胞瘤模型。该模型产生了多层肿瘤细胞侵入腹膜表面，并用于模拟患者胶质母细胞瘤（GBM）切除后剩余的术后手术腔。发现罗丹明标记的DMRIE/DOPE + DNA复合物穿透至少20个肿瘤细胞层。肿瘤形成后腹腔注射p53基因/脂质体复合物导致肿瘤大量坏死。在坏死病变附近的肿瘤细胞中发现使用DO-1抗体的人p53蛋白的显著染色。肿瘤外植体表达人p53蛋白，并且在体外生长测定中显示出54%的生长减少。此外，与载体对照相比，DMRIE/DOPE介导的p53基因转染显著增加了荷瘤小鼠的平均存活时间。这些结果表明，通过脂质体介导的转染方法，使用外源性野生型p53在体内抑制具有内源性野生型p53的胶质母细胞瘤细胞的效率。
A cavitary glioblastoma model was created by injection of RT-2 cells, which express endogenous wild type p53, into the peritoneal cavity of nude mice. This model developed multiple layers of tumor cells invading the peritoneal surface and was used to mimic the postoperative surgical cavity remaining after glioblastoma (GBM) excision in patients. Rhodamine labeled DMRIE/DOPE + DNA complexes were found to penetrate at least 20 tumor cell layers. Injection of p53 gene/liposome complexes into the intraperitoneal cavity after the tumor was established resulted in massive tumor necrosis. Prominent staining of human p53 protein using the DO-1 antibody was found in tumor cells near the necrotic lesions. Tumor explants expressed human p53 protein and showed a 54 % growth reduction in an in vitro growth assay. Further, DMRIE/DOPE mediated p53 gene transfection significantly increased the mean survival time of tumor bearing mice compared to vector control. These results demonstrate the efficiency of using exogenous wild type p53 to suppress glioblastoma cell with endogenous wild type p53 in vivo through liposome mediated transfection method.