Effect of HSP90 inhibitor in pheochromocytoma PC12 cells: an experimental investigation

Yunze Xu, Chongyu Zhang, Dongning Chen, Juping Zhao, Zhoujun Shen, Yuxuan Wu, Yu Zhu
Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine 2013, 34 (6): 4065-71
This study aims to investigate whether the expression of heat shock protein 90 (HSP90) is associated with the malignant pheochromocytoma (PHEO) and the effects of 17-allylamino-17-demethoxygeldanamcyin (17-AAG) on the expression of vascular endothelial growth factor (VEGF) in PHEO cell line PC12. The expression of HSP90 was investigated in 38 paraffin-embedded samples of PHEO patients using immunohistochemistry. The time and concentration effects of 17-AAG were investigated in PHEO PC12 cells. Cell proliferation was measured by MTT assay and cell counting. Apoptosis was detected by flow cytometry. Positive staining for HSP90 was found in 14 of 17 malignant (82.35%) and in 5 of 21 (23.81%) benign PHEOs. There existed a significant statistical difference between the malignant group and the benign ones (P < 0.001). 17-AAG inhibited the proliferation of HCC cells in a time- and concentration-dependent manner. The apoptosis rates of PC12 cells after treatment with 0.1 μmol/L for 6, 12, 24, and 48 h were significantly higher than that in blank control group. 17-AAG significantly downregulated VEGF-165 protein level in PC12 cells. This study has confirmed that the specific HSP90 inhibitor 17-AAG can play a therapeutic role in malignant PHEO treatment, and HSP90 qualifies as a promising new target in malignant PHEO.

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