Takahashi M, Kigawa J, Minagawa Y, Itamochi H, Shimada M, Kamazawa S, Sato S, Akeshima R, Terakawa N
Department of Obstetrics and Gynecology, Tottori University, School of Medicine, 36-1 Nishimachi, 683-8507, Yonago, Japan.
Eur J Cancer. 2000 Sep;36(14):1863-8. doi: 10.1016/s0959-8049(00)00183-0.
We conducted this study to determine whether the sensitivity of ovarian cancer cells to paclitaxel (PTX) relates to cells undergoing p53-dependent apoptosis. Human ovarian adenocarcinoma cell lines (SK-OV-3, KF and KP cells) were used in this study. In SK-OV-3 and KP cells, which have a homozygous deletion of the TP53 gene, wild-type TP53 gene-transduction markedly enhanced the sensitivity to cisplatin (CDDP), but did not enhance the sensitivity to PTX. In all cells, the apoptotic index was increased by CDDP or PTX. After exposure to CDDP, p53 and Bax protein expression increased and Bcl-xL expression decreased in the KF cells and TP53 gene-transducted SK-OV-3 cells. However, these proteins did not change in KP cells. Therefore, the role of p53 in CDDP-induced apoptosis depends upon the cell type. In contrast, TP53 gene status did not correlate with PTX-induced cytotoxicity in any of the cell lines with differing apoptotic pathways. In conclusion, the sensitivity to PTX may not be related to p53-dependent apoptosis in ovarian cancer cells.
我们开展这项研究以确定卵巢癌细胞对紫杉醇(PTX)的敏感性是否与经历p53依赖性凋亡的细胞有关。本研究使用了人卵巢腺癌细胞系(SK-OV-3、KF和KP细胞)。在TP53基因纯合缺失的SK-OV-3和KP细胞中,野生型TP53基因转导显著增强了对顺铂(CDDP)的敏感性,但未增强对PTX的敏感性。在所有细胞中,CDDP或PTX均可增加凋亡指数。KF细胞和转导了TP53基因的SK-OV-3细胞在暴露于CDDP后,p53和Bax蛋白表达增加,Bcl-xL表达降低。然而,这些蛋白在KP细胞中没有变化。因此,p53在CDDP诱导的凋亡中的作用取决于细胞类型。相反,在具有不同凋亡途径的任何细胞系中,TP53基因状态与PTX诱导的细胞毒性均无相关性。总之,卵巢癌细胞对PTX的敏感性可能与p53依赖性凋亡无关。