Sensitivity to the non-COX inhibiting celecoxib derivative, OSU03012, is p21(WAF1/CIP1) dependent.
Sensitivity to the non-COX inhibiting celecoxib derivative, OSU03012, is p21(WAF1/CIP1) dependent.
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DOI：
10.1002/ijc.23895
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发表时间：
2008-12-15
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
OSU 03012是一种非COX抑制性塞来昔布衍生物，在许多癌细胞系中具有生长抑制和凋亡活性。为探讨OSU 03012对人口腔上皮细胞株TE 1177的生长抑制和凋亡作用中细胞周期蛋白的作用机制，采用HPV 16 E6（TE/E6）、HPV 16 E7（TE/E7）和空载体（TE/V）转化人口腔上皮细胞株TE 1177。显示低水平p53和不可检测水平p21 WAF 1/CIP 1的TE/E6细胞系对OSU 03012的生长抑制和凋亡作用敏感。TE/E7细胞系表达低水平的Rb和高水平的p53和p21 WAF 1/CIP 1耐药。OSU 03012减少了具有完整p53-p21 WAF 1/CIP 1检查点的TE/E7和TE/V细胞系的S期细胞数，但在检查点缺陷的TE/E6细胞系中不减少。OSU 03012处理还显著降低TE/E7和TE/V中的细胞周期蛋白A和Cdk 2的水平，但在TE/E6细胞系中没有，TE/E6细胞系具有显著增强的细胞周期蛋白A和Cdk 2的基础水平。与TE/E6细胞系一致，p21 WAF 1/CIP 1 −/−小鼠胚胎成纤维细胞对OSU 03012诱导的细胞凋亡更敏感，如PARP和caspase 3裂解所证明。这些数据表明，p21 WAF 1/CIP 1是细胞对OSU 03012的生长抑制和凋亡作用的敏感性的重要因素。
OSU03012 is a non-COX inhibiting celecoxib derivative with growth inhibiting and apoptotic activity in many cancer cell lines. To investigate mechanisms related to cell cycle proteins in growth inhibition and apoptosis induced by OSU03012, the primary human oral epithelial cell line, TE1177, was transformed with HPV16 E6 (TE/E6), HPV16 E7 (TE/E7) or empty vector (TE/V). TE/E6 cell lines exhibiting low levels of p53 and undetectable levels of p21WAF1/CIP1 were sensitized to the growth inhibiting and apoptotic effects of OSU03012. The TE/E7 cell lines expressing low levels of Rb and elevated levels of p53 and p21WAF1/CIP1 were resistant. OSU03012 reduced the number of cells in the S phase of the TE/E7 and TE/V cell lines with intact p53-p21WAF1/CIP1 checkpoint, but not in the checkpoint defective TE/E6 cell lines. Treatment with OSU03012 also markedly reduced the levels of cyclin A and Cdk2 in TE/E7 and TE/V, but not in TE/E6 cell lines, which had significantly enhanced basal levels of cyclin A and Cdk2. Consistent with the TE/E6 cell line, p21WAF1/CIP1−/− mouse embryo fibroblasts were more sensitive to OSU03012-induced apoptosis as evidenced by PARP and caspase 3 cleavages. These data suggest that p21WAF1/CIP1 is an important factor in the sensitivity of cells to the growth inhibiting and apoptotic effects of OSU03012.
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影响因子：
6.1
作者：
Lee, H;Li, D;Milo, GE
通讯作者：
Milo, GE
DOI：
10.1073/pnas.87.4.1268
发表时间：
1990-02-01
影响因子：
11.1
作者：
MILO, GE;SHULER, C;TREWYN, RW
通讯作者：
TREWYN, RW
影响因子：
2.9
作者：
Han, CH;Ding, HM;D'Ambrosio, SM
通讯作者：
D'Ambrosio, SM
影响因子：
8
作者：
Lu, YJ;Yamagishi, N;Takebe, H
通讯作者：
Takebe, H
影响因子：
4
作者：
DARZYNKIEWICZ, Z
通讯作者：
DARZYNKIEWICZ, Z