In vitro cytotoxicity of cabazitaxel in adrenocortical carcinoma cell lines and human adrenocortical carcinoma primary cell cultures

Publication date: Available online 16 September 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Martina Fragni, Lilian Patricia Palma Lopez, Elisa Rossini, Andrea Abate, Deborah Cosentini, Valentina Salvi, Sara Vezzoli, Pietro Luigi Poliani, Daniela Bosisio, Constanze Hantel, Guido A.M. Tiberio, Salvatore Grisanti, Maurizio Memo, Massimo Terzolo, Alfredo Berruti, Sandra SigalaAbstractAdrenocortical cancer (ACC) is a rare and aggressive malignancy with a poor prognosis. The overall 5-year survival rate of patients with ENS@T stage IV ACC is less than 15%. Systemic antineoplastic therapies have a limited efficacy and new drugs are urgently needed.Human ACC primary cultures and cell lines were used to assess the cytotoxic effect of cabazitaxel, and the role of P-glycoprotein in mediating this effect.Cabazitaxel reduced ACC cell viability, both in ACC cell lines and in ACC primary cell cultures. Molecular and pharmacological targeting of ABCB1/P-gp did not modify its cytotoxic effect in NCI–H295R cells, while it increased the paclitaxel-induced toxicity. Cabazitaxel modified the expression of proteins involved in cellular physiology, such as apoptosis and cell cycle regulation. The drug combination cabazitaxel/mitotane exerted an additive/moderate synergism in different ACC cell experimental models. These results provide a rationale for testing cabazitaxel in a clinical study.
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research