VHL loss predicts response to Aurora kinase A inhibitor in renal cell carcinoma cells
| Autor: | Guang Chen, Jun Zhou, Xiao‑Fei Ding, Ying‑Liang Wu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Cancer Research
endocrine system diseases Cell Mice Nude urologic and male genital diseases Biochemistry chemistry.chemical_compound Mice Cell Line Tumor Genetics medicine Animals Humans neoplasms Molecular Biology Carcinoma Renal Cell Protein Kinase Inhibitors Aurora Kinase A Gene knockdown Mice Inbred BALB C Oncogene Chemistry Azepines Cell cycle Molecular medicine Xenograft Model Antitumor Assays female genital diseases and pregnancy complications Kidney Neoplasms Gene Expression Regulation Neoplastic medicine.anatomical_structure Pyrimidines Oncology Cell culture Von Hippel-Lindau Tumor Suppressor Protein Alisertib Cancer research Molecular Medicine |
| Zdroj: | Molecular medicine reports. 18(1) |
| ISSN: | 1791-3004 |
| Popis: | The majority of molecular targets of anticancer agents are limited to a subset of patients, and therefore identification of more specific biomarkers that can be used to improve clinical outcomes is of increasing interest. The present study showed that von Hippel‑Lindau tumor suppressor (VHL) tumor‑suppressor activity may influence the therapeutic response to Aurora kinase A (AURKA) inhibitors in human renal cell carcinoma (RCC). VHL protein (pVHL) expression was evaluated by immunoblotting in the human RCC cell lines CAKI, ACHN, 786‑O, 769‑P and A498. The anti‑tumor activities of alisertib, an AURKA‑specific chemical inhibitor, were detected by Cell Counting Kit‑8 assay in vitro and mouse xenograft model in vivo. Additionally, the VHL‑mediated anti‑tumor activity was assessed in 769‑P and CAKI cells via the loss or gain of VHL. The results revealed that VHL‑deficient 786‑O, 769‑P and A498 cells were sensitive to alisertib. By contrast, alisertib‑resistant CAKI and ACHN cells expressed the wild type VHL gene. In addition, rescue or knockdown of VHL was observed to increase or decrease alisertib anti‑proliferation activity, respectively, in RCC cells. The inverse correlation between the VHL gene expression profile and alisertib sensitivity was further confirmed in human cancer xenografts models. Taken together, these results suggested that VHL loss could potentially serve as a biomarker for predicting the efficacy of AURKA inhibitors. |
| Databáze: | OpenAIRE |
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