pEgr-IFNγ重组质粒辐射诱导表达及其抑瘤作用的实验研究

Experimental study on radiation-inducible expression and anti-tumor effect of pEgr-IFNγ recombinant plasmid

目的 探讨pEgr IFNγ重组质粒在接种B16黑色素瘤小鼠体内的辐射诱导表达及其抑瘤效应。方法 小鼠肿瘤局部注射脂质体包裹的重组质粒pEgr IFNγ后 36h ,接受不同剂量X射线照射 ,观察各组小鼠照射后不同时间肿瘤生长速率和平均存活时间 ,照射后第 3天用RT PCR法检测瘤内IFNγ转录水平 ,照射后第 1,3和 5天用ELISA法检测小鼠血清中IFNγ含量。结果 照射后第 3天重组质粒 +2 0Gy组瘤内IFNγ转录水平明显高于重组质粒组 ;照射后第 1,3天血清中IFNγ含量明显高于重组质粒组和对照组 ;照射后第 9～ 15天 ,4次 (质粒 +5Gy)组小鼠肿瘤生长速率明显低于重组质粒 +2 0Gy组 ,且平均生存时间明显延长。结论 多次基因 较小剂量放射治疗的抑瘤效应优于单次基因 较大剂量放射治疗 ;基因 放射治疗组可能通过诱导瘤内IFNγ表达增强 ,使血液中IFNγ浓度升高 ,从而提高荷瘤机体免疫功能和抗肿瘤能力。

Objective To study the radiation-inducible expression and the anti-tumor effect of pEgr-IFNγ recombinant plasmid in mice bearing melanoma. Methods The pEgr-IFNγ plasmid was injected locally into the tumor in the mice, and the tumors were irradiated with X-rays 36 hours later. The tumor growth rate at different times and mean survival period of the mice were observed. The IFNγ mRNA level in the tumor was detected with RT-PCR, 3 days after irradiation, and the concentration of IFNγ in the serum of the mice was detected by ELISA 1,3 and 5 days after irradiation. Results The IFNγ mRNA level in the tumor of mice in the gene-radiotherapy group was significantly higher than that in the reconmbinant plasmid group 3 days after irradiation. The IFNγ concentration in the serum of mice in the gene-radiotherapy group was higher than that in the recombinant plasmid group and the control group 1 and 3 days after irradiation. The tumor growth rate in the group of plasmid injection followed by 5 Gy irradiation for four times was significantly lower than that in the group of plasmid injection followed by 20 Gy irradiation 9-15 days after irradiation, and the mean survival period was also longer. Conclusions The anti-tumor effect of plasmid injection followed by lower dose irradiation for several times is better than that by higher dose irradiation. By inducing higher expression of IFNγ gene in the tumor, pEgr- IFNγ gene-radiotherapy could increase the concentration of IFNγ in the serum, and therefore the body's immunologic function and anti-tumor ability are enhanced.