The Studies In Vivo On The Treatment Of Human Lung Cancer By TK/CD Double Suicide Gene Under The Control Of CEA Promoter

Objective: To investigate the treatment efficiency of the double suicide gene therapy system on lung carcinoma and the security in vivo studies.Method: Use the method of reverse transcription PCR to confirm the expression of gene in SPC-A-1,SPC-A-1/TK+CD and SPC-A-1/pIRES-EGFP cells.The total of 30 mice were randomly divided into 6 groups then established the model of human lung carcinoma xenografts, including blank control group, PBS control group, empty vector control group, GCV treatment group ,5-FC treatment group, combined treatment group..After tumors reached 5mm in diameter,the study began.Nude mice in Groups were given peritoneal injection of PBS,GCV,5-FC, respectively. After 5 weeks, the antitumor efficacy was evaluated by tumor mean volume, weight and inhibition rate .Moreover,we evaluated cell apoptosis by TUNEL and transmission electron microscope(TEM),and used routine pathologic examination(H.E)to observe the tissue of heart, liver, kidney.Result:The reverse transcription PCR proved SPC-A-1,SPC-A-1/TK+CD and SPC-A-1/pIRES-EGFP cells are CEA positive cells. exogenous double suicide gene HSV-TK/CD are only expressed by SPC-A-1/TK+CD cells, which combined with prodrug GCV and (or) 5-FC can significantly inhibite CEA positive lung carcinoma xenografts. Cell apoptosis were evaluated by TUNEL technique and transmission electron microscope (TEM),suggesting the anti-tumor effect of HSV-TK/CD double suicide gene system is through leading tumor cells to apoptosis. No obvious side effects are found in the tissue of various organs in nude mice by routine pathologic examination.Conclusion: To investigate the security and the treatment efficiency of the double suicide gene therapy system in a mouse xenografts model of lung carcinoma,we confirmed the HSV-TK/CD double suicide gene combined with prodrug GCV and (or) 5-FC can significantly inhibite CEA positive lung carcinoma cells through inducing targeted cells to apoptosis. Meanwhile, there are no significant side effects in other organs of nude mice.