Abstract:
:Adrenocortical tumor (ACT) is a malignancy with a low incidence rate and the current therapy for advanced disease has a limited impact on overall patient survival. A previous study from our group suggested that elevated expression of aurora-A and aurora-B is associated with poor outcome in childhood ACT. Similar results were also reported for adult ACTs. The present in-vitro study shows that AMG 900 inhibits aurora kinases in adrenocortical carcinoma cells. AMG 900 inhibited cell proliferation in NCI-H295 cells as well as in the ACT primary cultures and caused apoptosis in the cell line NCI-H295. Furthermore, it potentialized the mitotane, doxorubicin, and etoposide effects on apoptosis induction and acted synergistically with mitotane and doxorubicin in the inhibition of proliferation. In addition, we found that AMG 900 activated Notch signaling and rendered the cells sensitive to the combination of AMG 900 and Notch signaling inhibition. Altogether, these data show that aurora kinases inhibition using AMG 900 may be an adjuvant therapy to treat patients with invasive or recurrent adrenocortical carcinomas.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Borges KS,Andrade AF,Silveira VS,Marco Antonio DS,Vasconcelos EJR,Antonini SRR,Tone LG,Scrideli CAdoi
10.1097/CAD.0000000000000504subject
Has Abstractpub_date
2017-07-01 00:00:00pages
634-644issue
6eissn
0959-4973issn
1473-5741journal_volume
28pub_type
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