Akeshima R, Kigawa J, Takahashi M, Oishi T, Kanamori Y, Itamochi H, Shimada M, Kamazawa S, Sato S, Terakawa N
Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishimachi, Yonago, 6838504, Japan.
Br J Cancer. 2001 Jun 1;84(11):1551-5. doi: 10.1054/bjoc.2001.1812.
We conducted the present study to determine the relationship between p53-dependent apoptosis and telomerase activity in ovarian cancer cells. A human ovarian adenocarcinoma cell line, SK-OV-3 that had homozygous deletion of the p53 gene was used in this study. Wild-type p53 genes were transducted to SK-OV-3 cells with a recombinant adenovirus that contained a wild-type p53 gene (AxCAp53). IC(50)to cisplatin (CDDP) was 12.9 microM for SK-OV-3 cells and 9.2 microM for p53 gene-transducted SK-OV-3 cells. The apoptotic index for cells with p53 gene transduction was significantly higher than cells without transduction. Additionally, p53 gene transduction significantly enhanced CDDP-induced apoptosis. Bax protein in SK-OV-3 cells did not differ before and after exposure to CDDP. In SK-OV-3 cells with transduction of the p53 gene, the expression of p53 and Bax proteins increased after exposure to CDDP. Expression of Bcl-xL decreased after exposure to CDDP in SK-OV-3 cells with and without transduction. The telomerase activity in SK-OV-3 cells with the p53 gene was significantly lower compared with the cells without the p53 gene. CDDP exposure did not affect telomerase activity and human telomerase reverse transcriptase (hTERT) expression in both cell lines. We suggest that the p53 gene may relate to telomerase activity, but that p53-dependent apoptosis does not affect the activity.
我们开展本研究以确定卵巢癌细胞中p53依赖的凋亡与端粒酶活性之间的关系。本研究使用了p53基因纯合缺失的人卵巢腺癌细胞系SK-OV-3。用携带野生型p53基因的重组腺病毒(AxCAp53)将野生型p53基因转导入SK-OV-3细胞。SK-OV-3细胞对顺铂(CDDP)的半数抑制浓度(IC50)为12.9微摩尔,而p53基因转导的SK-OV-3细胞对顺铂的IC50为9.2微摩尔。p53基因转导细胞的凋亡指数显著高于未转导细胞。此外,p53基因转导显著增强了顺铂诱导的凋亡。SK-OV-3细胞暴露于顺铂前后Bax蛋白无差异。在转导了p53基因的SK-OV-3细胞中,暴露于顺铂后p53和Bax蛋白的表达增加。在转导和未转导p53基因的SK-OV-3细胞中,暴露于顺铂后Bcl-xL的表达均降低。与未携带p53基因的细胞相比,携带p53基因的SK-OV-3细胞中的端粒酶活性显著降低。顺铂暴露对两种细胞系的端粒酶活性和人端粒酶逆转录酶(hTERT)表达均无影响。我们认为p53基因可能与端粒酶活性有关,但p53依赖的凋亡并不影响其活性。