The molecular chaperone heat shock protein 90 alpha (Hsp90??) has been recognized in various tumours including glioma.\r\nThis pilot study using a proteomic approach analyses the downstream effects of Hsp90 inhibition using 17-allylamino-17-\r\ndemethoxygeldanamycin (17AAG) and a short hairpin RNA (shRNA) oligonucleotide targeting hsp90?? (shhsp90??) in theU87-MG\r\nglioma cell line. Preliminary data coupled with bioinformatic analysis identified several known and unknownHsp90 client proteins\r\nthat demonstrated a change in their protein expression after Hsp90 inhibition, signifying an alteration in the canonical pathways of\r\ncell cycle progression, apoptosis, cell invasion, angiogenesis, and metastasis. Members of the glycolysis pathway were upregulated,\r\ndemonstrating increased dependency on glycolysis for energy source by the treated glioma cells. Upregulated proteins also include\r\nHsp70 and members of its family such as Hsp27 and gp96, thereby suggesting the role of Hsp90 co-chaperones in compensating\r\nfor Hsp90 function after Hsp90 inhibition. Considering Hsp70�s role in antiapoptosis, it was postulated that a combination therapy\r\ninvolving a multitarget approach could be carried out. Consequently inhibition of both Hsp90 and Hsp70 in U87-MG glioma cells\r\nresulted in 60% cell death indicating the importance of combination therapy for glioma therapeutics.
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