The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line
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New therapeutic targets are needed to fight cancer. Aurora kinases (AK) were recently identified as vital key regulators of cell mitosis and have consequently been investigated as therapeutic targets in preclinical and clinical studies. Aurora kinase inhibitors (AKI) have been studied in many cancer types, but their potential capacity to limit or delay metastases has rarely been considered, and never in adrenal tissue. Given the lack of an effective pharmacological therapy for adrenal metastasis and adrenocortical carcinoma, we assessed AKI (VX-680, SNS314, ZM447439) in 2 cell lines (H295R and SW13 cells), 3 cell cultures of primary adrenocortical metastases (from lung cancer), and 4 primary adrenocortical tumor cell cultures. We also tested reversan, which is a P-gp inhibitor (a fundamental efflux pump that can extrude drugs), and we measured AK expression levels in 66 adrenocortical tumor tissue samples. Biomolecular and cellular tests were performed (such as MTT, thymidine assay, Wright’s staining, cell cycle and apoptosis analysis, Western blot, qRT-PCR, and mutation analysis). Our results are the first to document AK overexpression in adrenocortical carcinoma as well as in H295R and SW13 cell lines, thus proving the efficacy of AKI against adrenal metastases and in the SW13 cancer cell model. We also demonstrated that reversan and AKI Vx-680 are useless in the H295R cell model, and therefore should not be considered as potential treatments for ACC. Serine/threonine AK inhibition, essentially with VX-680, could be a promising, specific therapeutic tool for eradicating metastases in adrenocortical tissue.
KeywordsVX-680 Aurora kinases Adrenal gland Metastasis Reversan SW13 cells Primary cell cultures Lung carcinoma
Aurora kinase inhibitors
non-aldosterone-secreting cortical adenomas
non-small-cell lung cancer
We thank Dr. Frances Coburn and Jillian Walton for text editing. This work was partially supported by the ENS@T-CANCER (European Network for the Study of Adrenal Tumors - grant agreement no. 259735), and the Associazione Italiana per la Ricerca Oncologica di Base (AIROB, Padova, Italy). All authors have read the journal’s authorship agreement and the manuscript has been read and approved by all named authors.
Compliance with ethical standards
All authors have read the journal’s policy on conflicts of interest and have none to disclose.
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