In vitro and in vivo evaluation of novel cationic liposomes utilized for cancer gene therapy.
Advanced peritoneal carcinomatoses is very difficult to treat. We have explored the potential therapeutic application of gene therapy using cationic liposomes in this disease. The lacZ gene was introduced in vitro into ovarian and endometrial cancer cells using cationic liposomes. The transfection efficiency was similar to that of commercially available liposomes in serum-free medium (11.0-20.9% vs. 5.4-26.0%). In serum-containing medium, the efficiency was 1.9-18.1%, which is comparable with the efficiency in serum-free medium. However, the efficiency of commercial liposomes decreased drastically to between 0.1% and 4.7% in the serum-containing medium. When cultured cells were transfected with the herpes simplex virus thymidine kinase (HSV-tk) gene and ganciclovir (GCV) was added, the anti-tumor effect of GCV was 47-640 times greater than when the same experiment was performed with lacZ gene. Evaluation of anti-tumor effect was performed with the MTT assay. In vivo, the HRA and mEIIL ascitic mice were treated with HSV-tk gene and GCV using the peritoneal route, a significant prolongation of the mean survival time was observed by Kaplan-Meier analysis (16-18 days and 15-30 days, respectively, p < 0.05). These results indicate a potential role for gene therapy in the treatment of advanced intraperitoneal carcinomatoses using the novel cationic liposomes.
Serikawa
Takehiro
T
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-Dori, Niigata, 951-8510, Japan.
Kikuchi
Akira
A
Sugaya
Susumu
S
Suzuki
Norio
N
Kikuchi
Hiroshi
H
Tanaka
Kenichi
K
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D002412:Cations; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004983:Ethanolamines / Q000737:chemistry*; D005260:Female; D015774:Ganciclovir / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D007763:Lac Operon; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009226:Myristates / Q000737:chemistry*; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods*
D000970:Antineoplastic Agents; D002412:Cations; D004983:Ethanolamines; D008081:Liposomes; D009226:Myristates; C478049:O,O'-detetradecanoyl-N-(alpha-trimethylammonioacetyl)diethanolamine chloride; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D013937:Thymidine Kinase; D015774:Ganciclovir