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Effect of HSP90 inhibitor in pheochromocytoma PC12 cells: an experimental investigation
Abstract:
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.
Insights
Heat shock protein 90 (HSP90) is significantly more expressed in malignant pheochromocytoma (PHEO) than benign forms. The HSP90 inhibitor 17-allylamino-17-demethoxygeldanamcyin (17-AAG) shows therapeutic potential by inhibiting proliferation and inducing apoptosis in PHEO cells.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Pheochromocytoma (PHEO) is a neuroendocrine tumor with varying degrees of malignancy.
- Heat shock protein 90 (HSP90) is a molecular chaperone implicated in cancer progression.
- Targeting HSP90 is a potential therapeutic strategy for various cancers.
Purpose of the Study:
- To investigate the association between heat shock protein 90 (HSP90) expression and pheochromocytoma (PHEO) malignancy.
- To evaluate the effects of 17-allylamino-17-demethoxygeldanamcyin (17-AAG), an HSP90 inhibitor, on PHEO cell proliferation, apoptosis, and vascular endothelial growth factor (VEGF) expression.
Main Methods:
- Immunohistochemistry was used to assess HSP90 expression in 38 PHEO patient samples (17 malignant, 21 benign).
- The PHEO cell line PC12 was treated with 17-AAG to assess time- and concentration-dependent effects on cell proliferation (MTT assay, cell counting) and apoptosis (flow cytometry).
- Vascular endothelial growth factor (VEGF)-165 protein levels were measured in PC12 cells following 17-AAG treatment.
Main Results:
- HSP90 expression was significantly higher in malignant PHEOs (82.35%) compared to benign PHEOs (23.81%) (P < 0.001).
- 17-AAG inhibited PC12 cell proliferation and significantly increased apoptosis rates in a time- and concentration-dependent manner.
- 17-AAG treatment led to a significant downregulation of VEGF-165 protein levels in PC12 cells.
Conclusions:
- Elevated HSP90 expression is associated with malignant pheochromocytoma.
- The HSP90 inhibitor 17-AAG demonstrates anti-proliferative and pro-apoptotic effects on PHEO cells, also downregulating VEGF.
- HSP90 represents a promising therapeutic target for malignant pheochromocytoma, with 17-AAG showing potential clinical utility.
