Pular para o conteúdo
Merck
  • Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment.

Co-Administration of Fendiline Hydrochloride Enhances Chemotherapeutic Efficacy of Cisplatin in Neuroblastoma Treatment.

Molecules (Basel, Switzerland) (2020-11-14)
Antonella Brizzolara, Patrizia Garbati, Serena Vella, Matilde Calderoni, Alessandro Quattrone, Gian Paolo Tonini, Mario Capasso, Luca Longo, Raffaella Barbieri, Tullio Florio, Aldo Pagano
RESUMO

Despite significant improvement of neuroblastoma (NB) patients' survival due to recent treatment advancements in recent years, NB is still associated with high mortality rate. In search of novel strategies to increase NB's susceptibility to pharmacological treatments, we investigated the in vitro and in vivo effects of fendiline hydrochloride as an enhancer of cisplatin antitumor activity. To assess the modulation of fendiline treatment on cisplatin responses, we used in vitro (evaluating NB cell proliferation by XCELLigence technology and colony formation, and gene expression by RT-PCR) and in vivo (NB cell grafts in NOD-SCID mice) models of NB. NB cell treatment with fendiline induced the expression of the ncRNA NDM29, leading to cell differentiation and to the reduction of the expression of MDRs/ABC transporters linked to multidrug resistance. These events were correlated to higher NB cell susceptibility to cisplatin and, consequently, increased its cytotoxic potency. In vivo, this drug interaction causes an enhanced ability of cisplatin to induce apoptosis in NB masses, resulting in tumor growth reduction and prolonged animal survival rate. Thus, the administration of fendiline might be a possible novel therapeutic approach to increase cisplatin efficacy in aggressive and poorly responsive NB cases.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
Anti-Disialoganglioside GD2 Antibody, clone 14G2a, clone 14.2Ga, Chemicon®, from mouse