p53 gene therapy of human osteosarcoma using a transferrin-modified cationic liposome.
Gene delivery via transferrin receptors, which are highly expressed by cancer cells, can be used to enhance the effectiveness of gene therapy for cancer. In this study, we examined the efficacy of p53 gene therapy in human osteosarcoma (HOSM-1) cells derived from the oral cavity using a cationic liposome supplemented with transferrin. HOSM-1 cells were exposed to transferrin-liposome-p53 in vitro, and the growth inhibition rate, expression of p53 and bax, and induction of apoptosis were measured 48 hours later. Treatment of HOSM-1 cells with transferrin-liposome-p53 resulted in 60.7% growth inhibition. Wild-type p53 expression and an increase in bax expression were observed following transfection with transferrin-liposome-p53, and 20.5% of the treated HOSM-1 cells were apoptotic. In vivo, the HOSM-1 tumor transplanted into nude mice grew to 5 to 6 mm in diameter. Following growth of the tumor to this size, transferrin-liposome-p53 was locally applied to the peripheral tumor (day 0) and then applied once every 5 days for a total of six times. During the administration period, tumor growth did not occur, and the mean tumor volume on the last day of administration (day 25) was 10.0% of that in the saline control group. These results suggest that p53 gene therapy via cationic liposome modification with transferrin is an effective strategy for treatment of osteosarcoma.
Nakase
Minoru
M
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Japan. nakase96@clin.medic.mie-u.ac.jp
Inui
Madoka
M
Okumura
Kenya
K
Kamei
Takahiko
T
Nakamura
Shinnosuke
S
Tagawa
Toshiro
T
D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D002412:Cations; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005260:Female; D018014:Gene Transfer Techniques; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D020287:In Situ Nick-End Labeling; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D010957:Plasmids / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; D002412:Cations; D008081:Liposomes; D019253:Proto-Oncogene Proteins c-bcl-2; D011990:Receptors, Transferrin; D014168:Transferrin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein