Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis
Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis
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DOI：
10.1006/excr.1998.4018
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发表时间：
1998-05-25
影响因子：
3.7
通讯作者：
Broggini, M
中科院分区：
文献类型：
--
作者：
Vikhanskaya, F;Vignati, S;Broggini, M
研究了紫杉醇对表达wt p53的人卵巢癌细胞株(A2780)和人乳头瘤病毒HPV16E6基因产物的亚克隆(A2780/E6)的细胞毒作用、细胞周期持续期和细胞凋亡的影响。通过检测紫杉醇诱导A2780/E6细胞p5 3和p2 1基因表达的能力，证实wt p5 3基因失活。P53阴性克隆(A2780/E6)对紫杉醇的敏感性约为表达P53的A2780细胞的50倍。这种敏感性的增加与紫杉醇诱导A2780/E6细胞周期中G2/M期细胞的强烈停滞有关，但与A2780细胞中的作用无关。这种不同的细胞周期停滞伴随着紫杉醇诱导的P53非依赖性细胞凋亡的频率增加，最初的研究倾向于排除ICE：和CPP32在诱导这些细胞凋亡中的直接作用，并显示出紫杉醇依赖的FLICE水平的增加，但其生物学相关性目前尚不明确。(C)1998年学术出版社。
Paclitaxel-induced cytotoxicity, cell cycle perdurbation, and apoptosis were determined in a human ovarian cancer cell Line expressing wt p53 (A2780) and in a subclone (A2780/E6) obtained upon transfection with the product of the E6 gene of the human papilloma virus HPV16. The inactivation of wt p53 in A2780/E6 was verified by measuring the inability of the clone to induce p53 and p21 expression after paclitaxel treatment. The p53-negative clone (A2780/E6) was approximately 50-fold more sensitive to paclitaxel than wt p53-expressing A2780 cells. This increased sensitivity was related to the ability of paclitaxel to induce a strong arrest of cells in the G2/M phase of the cell cycle in A2780/E6 but not in A2780 cells. This different cell cycle arrest was accompanied by increased frequency of paclitaxel-induced p53-independent apoptosis, Initial studies on proteases activation tend to exclude a direct role of ICE: and CPP32 in the induction of apoptosis in these cells and show a paclitaxel-dependent increase in FLICE levels, whose biological relevance is however at present not defined. (C) 1998 Academic Press.