HSP27 expression levels are associated with the sensitivity of hepatocellular carcinoma cells to 17-allylamino-17-demethoxygeldanamycin.

UNLABELLED: 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.
RESULTS: 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.
CONCLUSION: 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.