Shimada M, Kigawa J, Kanamori Y, Itamochi H, Takahashi M, Kamazawa S, Sato S, Terakawa N
Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishimachi, 6838504, Yonago, Japan.
Eur J Cancer. 2000 Sep;36(14):1869-75. doi: 10.1016/s0959-8049(00)00161-1.
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.
为阐明携带野生型TP53基因的重组腺病毒（AxCATP53）与顺铂（CDDP）联合治疗的效果，我们研究了有或无野生型TP53基因的卵巢癌异种移植瘤中p53依赖的细胞凋亡情况。将严重联合免疫缺陷（SCID）小鼠植入由无TP53基因的SK-OV-3细胞和有TP53基因的KF细胞组成的卵巢癌细胞系。在SK-OV-3和KF肿瘤中，与单独使用CDDP或单独使用AxCATP53单一治疗相比，联合治疗对肿瘤生长的抑制作用显著。联合治疗后，SK-OV-3肿瘤中的凋亡指数显著增加。SK-OV-3肿瘤中Bax蛋白的表达较弱，但在TP53基因转染后增强。相反，AxCATP53转染不影响KF肿瘤中CDDP诱导的细胞凋亡。因此，AxCATP53与CDDP联合治疗可能是治疗有或无TP53基因的卵巢癌的一种新策略。
