Increased efficiency of cisplatin-resistant cell lines to DNA-mediated gene transfer with cationic liposome.
OBJECTIVE
Because of its effectiveness against many gynecologic malignancies, chemotherapy including cisplatin is mainly used as the first-line chemotherapy for epithelium ovarian cancer. However, one of the major problems that is well recognized is that tumor cells can easily acquire resistance to cisplatin. Various trials were carried out in order to establish treatment against cisplatin-resistant tumor cells.


METHODS
Using both in vivo and in vitro studies, we examined whether or not the newly developed liposome could be used to demonstrate sufficient transfection activity as the anticancer reagent for cisplatin-resistant tumor cells.


RESULTS
With our newly developed liposome, GTE 319 and GTE 321, the lac-Z gene was more efficiently transfected in cisplatin-resistant variant cells, mEIIL-R, KF-ra and KF-rb, than in parental cells, mEIIL and KF, using X-gal staining. In cytotoxic assay, transfection of herpes simplex thymidine kinase (HSV-tk) gene conjugated with GTE319 or GTE 321, and cultivation with aciclovir for 5 days revealed accelerated tumor-inhibition activity in all of the cisplatin-resistant tumor cells compared with that in the naive parental cells. In addition, the high anti-tumor effect was obtained from intratumoral local injection of the tk gene conjugated with GTE-321 liposome following aciclovir administration against KF-rb-transplanted tumor formed in nude mouse hypodermic.


CONCLUSIONS
These results suggest that gene therapy using a newly developed liposome-conjugated suicide gene can be an attractive approach for treatment against cisplatin-resistant ovarian cancer cells.
Sato
Takaaki
T
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.
Serikawa
Takehiro
T
Sekine
Masayuki
M
Aoki
Yoichi
Y
Tanaka
Kenichi
K
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D009226:Myristates / Q000008:administration & dosage*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D013047:Specific Pathogen-Free Organisms; D014162:Transfection
D004983:Ethanolamines; D008081:Liposomes; D009226:Myristates; C478049:O,O'-detetradecanoyl-N-(alpha-trimethylammonioacetyl)diethanolamine chloride; D002945:Cisplatin; D000212:Acyclovir