Abstract:
Objective To investigate the antitumor effect of genetherapy in situ of carcinoembryonic antigen (CEA) tissue-specific cytosine deaminase (CD) /5-fluorocytosine (5-FC) system on human colorectal carcinoma in nude mice. Methods Recombinant ret roviral vector G1CEACDNa was packaged in PA317 cells with lipofectamine technique and then the cells were selectively cultured in G418 and the viral supernatant was harvested. The human colorectal carcinoma cell lines LoVo and SW480 were injected into flanking Balb/c nude mice respectively. 0. 2ml viral supernatant was injected into tumors daily for 3ds and 500 mg/ kg 5-FC was givenip daily for 21ds when the tumors were palpable. All the mice were sacrificed at the end of the t reatment, and then PCR and RT-PCR were performed to detect the expression of targeted gene in carcinoma tissue. Results The virus titer of G1CEACDNa was 5. 6 ×10
6 CFU (colony forming unit, CFU ) / L. The targeted genes were detected in tumor tissues. The weight of the LoVo cell tumor were 111. 52 ±25. 89 mg ( P < 0. 01, t = 4. 035, n = 5 than that in the cont rol group s) and the weight of the SW480 cell tumor were 685. 44 ±240. 38mg ( P < 0. 01, t = 3. 670, n = 5 than that in the parent groups) following administ ration of 5-FC systemically. Conclusion The CEA tissue-specific CD/5-FC system has an obvious targeting anti-tumor effect on human colorectal carcinoma LoVo cell tumor and SW480 cell tumor, but the killing effect on the LoVo cell tumor is stronger than that on the SW480 cell tumor.