Witt O, Schulze S, Kanbach K, Roth C, Pekrun A
Children's hospital, University of Göttingen, Robert-Koch-Street 40, D-37075 Göttingen, Germany.
Cancer Lett. 2001 Oct 10;171(2):173-82. doi: 10.1016/s0304-3835(01)00628-0.
The present study shows that stress signaling plays a role in differentiation of K562, PANC1, HT29 and HL60 tumor cells: (1) Butyrate induced differentiation in K562, PANC1, and HT29 cells can be inhibited by SB203580, a specific inhibitor of p38 stress activated protein kinase. (2) Heat shock and hyperosmolarity increase expression of differentiation markers in K562, HT29, HL60 and in K562, PANC1, and HT29 cells, respectively. (3) Conversely, environmental stress induced differentiation in K562, HT29, and PANC1 cells can be inhibited by SB203580 and quercetin, a compound with heat shock pathway inhibiting activity. (4) Butyrate and environmental stress enhance either additively or synergistically differentiation of K562, HT29, PANC1 or HL60 cells, respectively. Stress signaling pathways might be an interesting pharmacologic target for differentiation therapy of malignant disease.
本研究表明，应激信号在K562、PANC1、HT29和HL60肿瘤细胞的分化中起作用：（1）丁酸盐诱导的K562、PANC1和HT29细胞分化可被p38应激激活蛋白激酶的特异性抑制剂SB203580抑制。（2）热休克和高渗分别增加K562、HT29、HL60细胞以及K562、PANC1和HT29细胞中分化标志物的表达。（3）相反，SB203580和具有热休克途径抑制活性的化合物槲皮素可抑制环境应激诱导的K562、HT29和PANC1细胞分化。（4）丁酸盐和环境应激分别以相加或协同的方式增强K562、HT29、PANC1或HL60细胞的分化。应激信号通路可能是恶性疾病分化治疗中一个有趣的药理学靶点。
