Effects of the novel heat shock protein 90 inhibitor AUY922 in renal cell carcinoma ACHN and 786-O cells

Abstract

Abstract. The aim of the present study was to investigate the effects of the heat shock protein (HSP)90 inhibitor AUY922 on the proliferation and migratory ability of renal cell carcinoma (RCC) cells. The expression of HSP90 was measured in vitro using western blotting and quantitative polymerase chain reaction in the ACHN and 786-O cell RCC lines, and also in the immortalized normal human proximal tubule epithelium HK-2 cell line. The effects of the time and concentration of AUY922 administration were investigated in the ACHN and 786-O cells, and the cell proliferation was measured using an MTT assay. A Transwell assay was performed to evaluate the migratory ability of ACHN cells following treatment with AUY922 at concentrations of 10, 50 and 100 nM. Western blot analysis and reverse transcription polymerase chain reaction revealed that HSP90 mRNA and protein were overexpressed in the two RCC cell lines compared with the HK-2 cell line. AUY922 inhibited the proliferation of the ACHN and 786-O cells in a time-and concentration-dependent manner, and the migratory ability of the ACHN cells was markedly suppressed subsequent to treatment with AUY922. The present data suggest that the pathogenesis of human RCC may be mediated by HSP90. It was also indicated that the specific HSP90 inhibitor AUY922 plays a therapeutic role in the treatment of RCC, and therefore, HSP90 may be a selective target for molecular-targeted treatments of RCC.

Radiation induces premature chromatid separation via the miR-142-3p/Bod1 pathway in carcinoma cells

“…Renal cell carcinoma, a lethal urologic malignancy that originates in renal tubular epithelial cells, comprises approximately 90% of all kidney cancers and accounts for 2-3% of all cancers worldwide [ 46 , 47 ]; lung cancer is the second most common type of cancer worldwide, with approximately 1.6 million new cases diagnosed each year, and the leading cause of cancer-related death, estimated at 1.37 million annually [ 48 , 49 ]. Radiotherapy is a crucial component of treatment for these and most other types of cancer, and treatments that increase radiosensitivity in resistant tumor cells would help improve the efficacy of radiotherapy [ 50 , 51 ].…”

The role of HSP90 molecular chaperones in hepatocellular carcinoma

“…HSP90 makes the mutated oncoproteins able to avoid misfolding and degradation and permits the malignant transformation (Barrott & Haystead, 2013; Wu et al, 2017). HSP90 promotes the growth and inhibits apoptosis in multiple types of cancers, such as bladder carcinoma (Lebret et al, 2003), medulloblastoma (Alexiou et al, 2013), renal (Zhu, Zhu, Qi, & Qiu, 2015), lung (Esfahani & Cohen, 2016), colorectal (Moser et al, 2007), and acute leukemia (Tian et al, 2014) as well as HCC (Dong, Xue, et al, 2018; C. Wang, Zhang, et al, 2016). More recently, it was shown that the HSP90 is a potential biomarker of HCC, and the diagnostic value of its expression for HCC detection was reported (Wei et al, 2020).…”