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)联合放疗、化疗药物和热疗的体内潜在的肿瘤抑制作用。所研究的肿瘤细胞系来自小鼠自发性纤维肉瘤FSA-11。分别用pSV2-neo载体(neo系)或MnSOD与pSV2-neo共转染细胞(SOD系)。所用细胞系为高表达MnSOD活性的细胞系，并以NEO为对照。体外有氧照射时，SOD-H细胞系对~(60)Co伽马射线的耐受性略高于NEO细胞系。而SOD-H和NEO对290 MeV/u碳束的辐射敏感性几乎相同。这些数据与以前的TCD50数据进行了分析，即控制一半受照射肿瘤的辐射剂量。该分析预测，在氧气条件下，碳束照射的NEO和SOD-H的TCD50值分别为7.1Gy值和3.0Gy值。对体外MMC处理，SOD-H细胞比NEO细胞具有更强的抗性。SOD-H对ADR的体内效应与NEO几乎相同，但对ADR和5FU的体外效应略高于NEO。因此，预测MnSOD活性的提高可能会增强放射、化疗药物5FU和MMC的体内效应。根据这些预测数据，体内MnSOD基因转染和放化疗的多学科治疗正在进行中。

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.