In vivo study on the effect of adenovirus mediating Smad 7 gene expression regulated by radiation via Egr-1 promoter in C57BL mice implanted with Lewis lung cancer / 中华放射肿瘤学杂志

ABSTRACT

Objective Objective To study the effect of adenovirus mediating Smad 7 gene regulated by radiation via Egr-1 on the primary tumor and lung metastasis in C57BL mice implanted with Lewis lung cancer.Methods The radio-inducible elements from the Egr-1 gene promoter were inserted upstream to a cDNA encoding Smad7 and integrated into a replication-defective adenovirus to generate recombinant adenovirus(AD.Egr-Smad 7).270 mice implanted with Lewis lung cancer in the hind legs were used and the experiment was started when the transplanted tumor diameter reached 0.8 to 1.0cm.Then three investigations were undertaken,each demanding 90 mice implanted with Lewis lung cancer respectively.To each group,90 mice models were randomized into 3 groups the normal control group;the NS control group;and the implanted AD.Egr-Smad 7 group.Every 6 mice in each group were irradiated by different single dose to study the following 1.The maximal and minimal diameters of the tumor were recorded to observe the tumor growth tendency,the tumor growth delay and the mice survival time,2.The incidence of lung metastasis two weeks after the radiation was recorded.3.The incidence of lung metastasis when the tumor volume was four times as large as that at the beginning of radiation was recorded.Results The adenovirus mediating Smad 7 gene expression regulated by irradiation via Egr-1 in C57BL mice implanted with Lewis lung cancer was able to inhibit the progression of the primary tumor and prolong the survival of the mice significantly as compared with the control group(P0.05).Conclusions The gene expression of AD.Egr-Smad 7 regulated by radiation is not risky in promoting the local progression and distant metastasis of Lewis lung cancer in mice.On the other hand,the gene expression of AD.Egr-Smad 7 regulated by radiation could inhibit the progression of the primary tumor and prolong the survival time of the mice significantly.It is safe,to some extent,of using AD.Egr-Smad 7 to block the signal transduction of TGF-?locally as a novel strategy for gene therapy aiming at the prevention of radiation-induced lung