Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Future Oncol. 2013 Mar;9(3):411-8. doi: 10.2217/fon.13.2.
AIMS, MATERIALS & METHODS: As heat-shock proteins are associated with tumor proliferation, differentiation, invasion and metastasis, we investigated whether targeting Hsp90 with the geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17AAG) can inhibit the viability of hepatocellular carcinoma cell lines with various levels of metastatic potential. In addition, we investigated whether the use of Hsp27-siRNA can decrease resistance to 17AAG.
Although 17AAG upregulated the expression of heat-shock proteins, it did not affect the expression of Hsp90 client proteins in normal hepatocytes. Hsp90 inhibition by 17AAG degraded its client proteins in both low- and high-metastatic potential cell lines. siRNA inhibited Hsp27 expression in cell lines and improved the sensitivity of 17AAG.
17AAG inhibited the viability of hepatocellular carcinoma cells by degrading Hsp90 client proteins. The sensitivity of cells to 17AAG is associated with the level of Hsp27 expression.
目的、材料和方法：由于热休克蛋白与肿瘤增殖、分化、侵袭和转移有关，我们研究了用格尔德霉素衍生物 17-烯丙氨基-17-去甲氧基格尔德霉素（17AAG）靶向 Hsp90 是否可以抑制具有不同转移潜能的肝癌细胞系的活力。此外，我们还研究了使用 Hsp27-siRNA 是否可以降低对 17AAG 的耐药性。
尽管 17AAG 上调了热休克蛋白的表达，但它不会影响正常肝细胞中 Hsp90 客户蛋白的表达。17AAG 通过抑制 Hsp90 降解了低转移潜能和高转移潜能细胞系中的客户蛋白。siRNA 抑制了细胞系中 Hsp27 的表达，并提高了 17AAG 的敏感性。
17AAG 通过降解 Hsp90 客户蛋白抑制肝癌细胞的活力。细胞对 17AAG 的敏感性与 Hsp27 表达水平相关。
