Mechanism of the combination effect of wild-type TP53 gene transfection and cisplatin treatment for ovarian cancer xenografts.
To clarify the effect of a combination treatment consisting of a recombinant adenovirus carrying a wild-type TP53 gene (AxCATP53) and cisplatin (CDDP), we examined p53-dependent apoptosis in ovarian cancer xenografts with and without the wild-type TP53 gene. Severe combined immunodeficiency (SCID) mice were implanted with ovarian cancer cell lines consisting of SK-OV-3 cells without the TP53 gene and KF cells with the TP53 gene. In SK-OV-3 and KF tumours, the inhibitory effect of the combination treatment on tumour growth was significant, compared with a single treatment with CDDP alone or AxCATP53 alone. The apoptotic index increased significantly after combination treatment in the SK-OV-3 tumours. The expression of Bax protein in SK-OV-3 tumours was weak, but strengthened after TP53 gene transfection. In contrast, AxCATP53 transfection did not affect CDDP-induced apoptosis in the KF tumours. Therefore, combination treatment of AxCATP53 and CDDP may be a new strategy for treating ovarian cancer with or without the TP53 gene.
Shimada
M
M
Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishimachi, 6838504, Yonago, Japan.
Kigawa
J
J
Kanamori
Y
Y
Itamochi
H
H
Takahashi
M
M
Kamazawa
S
S
Sato
S
S
Terakawa
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection / Q000379:methods*; D014170:Transformation, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002945:Cisplatin