Nonviral gene delivery to human ovarian cancer cells using arginine-grafted PAMAM dendrimer.
BACKGROUND
A specific and effective strategy is in demand to treat ovarian cancer successfully. Epidermal growth factor receptor (EGFR) is highly expressed in ovarian cancer, and thus EGFR antisense gene therapy can be a potential therapeutic strategy.


METHODS
L-Arginine-grafted-polyamidoamine dendrimer (PAMAM-Arg) has been reported to be a novel nonviral gene delivery carrier. Therefore, the ability of PAMAM-Arg in transferring a luciferase gene to ovarian carcinoma SK-OV3 cells has been examined, and the cytotoxicity of the cationic polymer has been investigated. In addition, the suppression of cell proliferation has been evaluated by transferring an EGFR antisense gene to SK-OV3 cells using PAMAM-Arg. Polyethyleneimine (PEI) 25K was used as a positive control.


RESULTS
As a result, in vitro gene transfection efficiency of PAMAM-Arg was enhanced with increasing transfection time and N/P ratios. PAMAM-Arg transferred the luciferase gene into cells more efficiently than PEI. In addition, PAMAM-Arg was minimally toxic to the cells whereas PEI 25K was highly toxic. The polyplexes formed by the EGFR antisense gene and PAMAM-Arg significantly reduced thymidine incorporation into the cells suggesting the suppression of cancer cell proliferation.


CONCLUSIONS
These results suggest that a PAMAM-Arg/EGFR antisense gene complex can be used as a safe and efficient therapeutic agent for cancer gene therapy.
Division of Life and Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
Soo Hyun
SH
Jang
Su Jin
SJ
Choi
Ji Hyun
JH
Oh
Song Wha
SW
Chae
Kihoon
K
Nam
Jong Sang
JS
Park
Hwa Jeong
HJ
Lee
D001120:Arginine / Q000008:administration & dosage / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D016373:DNA, Antisense / Q000235:genetics; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008958:Models, Molecular; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000628:therapy*; D011094:Polyethyleneimine / Q000737:chemistry; D013936:Thymidine / Q000737:chemistry; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D050091:Dendrimers; C104700:PAMAM Starburst; D011094:Polyethyleneimine; D001120:Arginine; D008156:Luciferases; D066246:ErbB Receptors; D013936:Thymidine