The Basic Study for Mn-SOD Gene Therapy

本研究的目的是检测人锰超氧化物歧化酶（MuSOD）在放射、化疗和热疗联合治疗中的体内潜在肿瘤抑制作用。所研究的肿瘤细胞是来源于小鼠自发性纤维肉瘤FSa-ll的体外细胞系。用pSV2-NEO质粒转染（NEO系）或MnSOD质粒加pSV2-NEO质粒共转染（SOD系）。转染后表达高MnSOD活性的细胞系为SOD-H，对照组为NEO。体外氧照射下，SOD-H细胞株对^<60>Co γ射线的抗性略高于NEO细胞株。而SOD-H和NEO对290MeV/u碳束的辐射灵敏度几乎相同。这些数据与之前的TCD50数据进行了分析，TCD50是控制一半受照射肿瘤的辐射剂量。该分析预测氧化条件下NEO和SOD-H的TCD50值分别为7.1 Gy和3.0 Gy。SOD-H细胞株比NEO细胞株对体外MMC的抗性更强。SOD-H对ADR的体内作用与NEO几乎相同，但SOD-H对ADR和5FU的体外作用略高于NEO。因此，预测MnSOD活性的升高可能会增强5FU和MMC等放射、化疗药物的体内作用。根据这些预测数据，目前正在进行MnSOD基因转染和放化疗的体内多学科治疗。

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.