[Experimental treatment for human colorectal carcinoma by tissue type specific expression of herpes simplex virus thymidine kinase gene].
An expression plasmid pCEA-TK, in which HSV-TK gene was under the control of CEA promoter, was constructed. The human colorectal carcinoma cell line LoVo or the human uterine cervical cancer cell line HeLa was co-transfected with pSV2-neo and pCEATK, respectively. After G418 selection, both transgenic cell clones (LoVo/CEATK and HeLa/CEATK) were obtained. LoVo/CEATK cells were 1300 times more sensitive to the cytotoxicity of ganciclovir than LoVo cells. However, the elevation of GCV sensitivity induced by pCEATK gene in HeLa line was only 8 times. Injection of GCV resulted in significant regression of HSV-TK transfected LoVo tumor in nude mice. These data suggested that the expression of TK gene driven by CEA promoter specifically killed CEA-positive colorectal carcinoma cells. Transmission electromicroscopy and DNA fragmentation assay demonstrated that GCV could induce apoptosis in LoVo/CEATK cells. The possibility of the CEATK/GCV system in the treatment of human colorectal carcinoma was discussed.
Ge
K
K
Shanghai Institute of Biochemistry, Chinese Academy of Sciences, Shanghai 200031.
Jiang
Q
Q
Xu
D H
DH
Zheng
Z C
ZC
Liu
X Y
XY
D000818:Animals; D017209:Apoptosis; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000473:pathology; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000737:chemistry; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D014162:Transfection; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D013937:Thymidine Kinase; D015774:Ganciclovir