Combined liposome-mediated cytosine deaminase gene therapy with radiation in killing rectal cancer cells and xenografts in athymic mice.
OBJECTIVE
The aim of this study was to assess the antitumor efficacy of combination of cytosine deaminase (CD) suicide gene therapy with radiation and to grope for new therapeutic strategy for local recurrent rectal cancer.


METHODS
HR-8348 cell line of human rectal cancer was used to assess efficiency of transfection with plasmid pEGFP-N1 and PXJ41-CD. The cells were exposed to radiation followed by liposome-mediated transfection. Cell inhibition assay was done with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Antitumor efficacy of combined liposome-mediated CD suicide gene therapy with radiation was determined by treatment of nude mice bearing HR-8348 cancer cell xenograft.


RESULTS
The efficiency of liposome-mediated CD gene transfection can be improved by radiation. With radiation at 2, 4, 6, and 8 Gy, the efficiency of liposome-mediated transfection increased from 21.3% to 62.2%, 78.0%, 83.2%, and 87.8%, respectively. CD expression was enhanced as well. Cancer cell inhibition experiment showed that combined liposome-mediated CD gene therapy with radiation had much stronger antitumor effect. With HR-8348 tumor xenograft model, suppression of tumor xenograft was observed. Compared with control group, tumor volume was inhibited by 81.5%, 48.5%, and 37.4%, respectively, in the combined CD/5-fluorocytosine with radiation group, CD/5-fluorocytosine group, and radiation group and the wet weight of tumor was decreased by 80%, 41.7%, and 37.7%, respectively.


CONCLUSIONS
These findings suggested that combination of liposome-mediated CD gene therapy with radiation is a safer and efficient anticancer method. Its therapeutic efficacy may meet clinical treatment on local recurrent rectal cancer.
Li
Shiyong
S
Department of General Surgery, General Hospital of Beijing Military Command, Beijing, China.
Yu
Bo
B
An
Ping
P
Chen
Gang
G
Lu
Wenping
W
Cai
Huiyun
H
Guo
Wenhua
W
Zuo
Fuyi
F
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D043525:Cytosine Deaminase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005437:Flucytosine / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010957:Plasmids / Q000235:genetics / Q000528:radiation effects; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000963:Antimetabolites; D008081:Liposomes; D005437:Flucytosine; D043525:Cytosine Deaminase