Abstract A294: Antitumor activity of AMG900, an Aurora kinase inhibitor, alone or in combination with chemotherapeutic agents on H295A adrenocortical carcinoma cell line.

Abstract

Pediatric adrenocortical tumors (ACT) are rare malignancies and in advanced disease the treatment has a small impact on overall survival. Previous study from our group suggests that AURKA and AURKB overexpression in pediatric ACT may be related to more aggressive disease. These genes are involved in the maintenance of the genome integrity during cell cycle division and they have been considered as new targets to cancer treatment. The present study shows the previous results of the effects of the new Aurora kinase inhibitor AMG900, associated or not with standard chemotherapeutic agents on adrenocortical carcinoma cell line H295A. Cell proliferation was assessed by Giemsa staining and apoptosis was performed by flow cytometry. Quantitative RT-PCR assays were used to determine the mRNA expression after AMG900 exposition. Drug combination analysis was made based on Chou-Talalay method. Hormones dosage assay was carried out to evaluate the effects of the Aurora kinase inhibitor on hormone secretion. AMG900 inhibited cell proliferation and caused apoptosis in a dose dependent manner in H295A cells. Moreover, it acted synergistically with doxorubicin, cisplatin and etoposide in the apoptosis induction, but only with doxorubicin in the proliferation inhibition. AMG900 treatment induced the mRNA expression of the genes p53, p21, and GDF15 and effectively inhibited dehydroepiandrosterone, androstenedione, cortisol and testosterone secretion. These data suggest that Aurora kinase inhibition by AMG900 may be a new therapeutic approach to adrenocortical carcinoma treatment. Financial Support: FAPESP (10/07020-9 and 12/09391-0) Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A294. Citation Format: Kleiton S. Borges, Augusto F. Andrade, Vanessa S. Silveira, David S.M Antonio, Elton J.R. Vasconcelos, Sonir R.R. Antonini, Luiz G. Tone, Carlos A. Scrideli. Antitumor activity of AMG900, an Aurora kinase inhibitor, alone or in combination with chemotherapeutic agents on H295A adrenocortical carcinoma cell line. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A294.