The Basic Study for Mn-SOD Gene Therapy

Mn-SOD基因治疗的基础研究

• 批准号: 08044290
• 负责人: KURODA Masahiro
• 金额: $ 0.83万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044290/
• 关键词: Mn-SOD; Radiation; Chemotherapy; Gene-therapy; Gene transfection; Multidisciplinary troatment

The objective of this study is to test the in vivo potential tumor suppressive effect of human manganese superoxide dismutase (MuSOD) for the combined treatments with radiation, chemotherapeutic agents and hyperthermia. Tumor cells studied were an in vitro line derived from a murine spontaneous fibrosarcoma, FSa-ll. These cells were transfected with pSV2-NEO plasmid (NEO line) or co-transfected with MnSOD plasmid plus pSV2-NEO plasmid (SOD line). The cell lines used was SOD-H,which expressed high MnSOD activities after transfection, and NEO as control. The SOD-H cell line was slightly more resistant to ^<60>Co gamma-ray than NEO cell line when irradiated in vitro in the presence of oxygen. However both SOD-H and NEO had the almost same radiosensitivity for 290MeV/u carbon beam. These data were analyzed with the previous data of TCD50, that is the radiation dose to control one-half of the irradiated tumors. This analysis predicted TCD50 values of NEO and SOD-H with carbon beam under oxic condition to be 7.1 Gy and 3.0 Gy, respectively. The SOD-H cell line was more resistant than NEO cell line for in vitro MMC treatment. The in vivo effect for ADR was almost same in SOD-H as in NEO,although in vitro effects for ADR and 5FU were slightly high in SOD-H than in NEO.As a result, it was predicted that the elevated activity of MnSOD might enhance the in vivo effects of radiation, chemotherapeutic agents such as 5FU and MMC.Following these predicted data, the in vivo multidisciplinary treatment with MnSOD gene-transfection and radiotherapy and chemotherapy are now on going.

本研究的目的是测试人锰超氧化物歧化酶（MuSOD）与放疗、化疗药物和热疗联合治疗的体内潜在肿瘤抑制作用。研究的肿瘤细胞是源自鼠自发性纤维肉瘤FSa-II的体外细胞系。将这些细胞用pSV 2-NEO质粒转染（NEO系）或用MnSOD质粒和pSV 2-NEO质粒共转染（SOD系）。用SOD-H细胞系转染后MnSOD活性高，NEO细胞系作为对照。SOD-H细胞对γ射线的耐受性略<60>高于NEO细胞。而SOD-H和NEO对290 MeV/u碳束的辐射敏感性几乎相同。这些数据与先前的TCD 50数据进行了分析，TCD 50是控制一半照射肿瘤的辐射剂量。该分析预测在好氧条件下碳束对NEO和SOD-H的TCD 50值分别为7.1戈伊和3.0戈伊。SOD-H细胞株对MMC的耐受性强于NEO细胞株。SOD-H对ADR的体内效应与NEO几乎相同，但对ADR和5 FU的体外效应略高于NEO。因此，预测MnSOD活性的升高可能会增强放射、化疗药物如5 FU和MMC的体内效应。目前正在进行MnSOD基因转染和放化疗的体内多学科治疗。