热休克蛋白 70 抑制增强了多柔比星诱导的间变性甲状腺癌细胞死亡。
Hsp70 inhibition potentiates radicicol-induced cell death in anaplastic thyroid carcinoma cells.
机构信息
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea
出版信息
Anticancer Res. 2014 Sep;34(9):4829-37.
BACKGROUND/AIM: The aim of the present study was to evaluate the effect of radicicol, an inhibitor of heat shock protein (hsp) 90, alone or in combination with hsp70 inhibition on survival of anaplastic thyroid carcinoma (ATC) cells.
MATERIALS AND METHODS
Antitumor activity of radicicol-alone or in combination with the hsp70 inhibitor VER155008 was investigated in 8505C and CAL62 cells.
RESULTS
Radicicol decreased cell viability and Akt protein levels, and increased the percentage of dead cells and hsp70 protein levels. In PIK3CA plasmid-transfected cells, compared to cells treated with radicicol-alone, cell viability increased and cellular death decreased. In cells treated with both radicicol and VER155008, compared to cells treated with radicicol-alone, cell viability further decreased and the percentage of dead cells further increased, with a parallel decrease of the protein levels of heat shock cognate 70, Akt and survivin.
CONCLUSION
Our results suggest that radicicol induces cell death mediated through PI3K/Akt signaling with modulation of hsp90 client proteins and hsp70 inhibition enhances radicicol-induced cell death with suppression of survivin in ATC cells.
背景/目的：本研究旨在评估热休克蛋白 90（hsp90）抑制剂雷地昔布单独或联合 hsp70 抑制对间变性甲状腺癌（ATC）细胞存活的影响。
材料和方法
在 8505C 和 CAL62 细胞中，研究了雷地昔布单独或与 hsp70 抑制剂 VER155008 联合的抗肿瘤活性。
结果
雷地昔布降低了细胞活力和 Akt 蛋白水平，增加了死亡细胞的百分比和 hsp70 蛋白水平。在 PIK3CA 质粒转染的细胞中，与雷地昔布单独处理的细胞相比，细胞活力增加，细胞死亡减少。与雷地昔布单独处理的细胞相比，同时用雷地昔布和 VER155008 处理的细胞，细胞活力进一步降低，死亡细胞的百分比进一步增加，热休克同源 70、Akt 和生存素的蛋白水平平行下降。
结论
我们的结果表明，雷地昔布通过 PI3K/Akt 信号通路诱导细胞死亡，同时调节 hsp90 客户蛋白，hsp70 抑制增强了雷地昔布诱导的 ATC 细胞死亡，并抑制了生存素。
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