Inhibition of the Hippo Signaling Pathway Component YAP in Neuroblastoma


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Kum Özşengezer S., Altun Z. S., Olgun H. N., Sanlav G.

56th Congress of the International Society of Paediatric Oncology (SIOP) , Hawaii, Amerika Birleşik Devletleri, 17 - 20 Ekim 2024, cilt.71, sa.158, ss.158, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 71
  • Doi Numarası: 10.1002/pbc.31444
  • Basıldığı Şehir: Hawaii
  • Basıldığı Ülke: Amerika Birleşik Devletleri
  • Sayfa Sayıları: ss.158
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Background and Aims: Neuroblastoma (NB) is a malignant tumor that is often seen in early childhood and originates from the sympathetic nervous system. Cisplatin (CDDP) is a widely used chemotherapeutic agent in the treatment of NB. YAP, the transcription co-activator of this pathway, is also an important part of this mechanism. Verteporfin (VP) is a light-sensitive benzoporphyrin derivative and is a potent and selective YAP inhibitor. Retinoic acid (RA) is a naturally occurring retinoid synthesized from vitamin A. The aim of this study is to reveal the potential anti-tumoral activity of VP, CDDP, RA and combinations of these agents in neuroblastoma through the Hippo pathway components in in-vitro and in-vivo conditions. Methods: In the study, the effects of VP, CDDP, RA and combinations of agents on apoptosis in N-MYC (-) SH-SY5Y and N-MYC (+) KELLY neuroblastoma cells were evaluated flow cytometrically with the Annexin-V/PI test. Additionally, by creating an NB xenograft model in nude mice using KELLY cells, the in-vivo anti-tumoral activities of the agents were examined based on tumor sizes. The relationship of the agents on the hippo pathway and stem cell differentiation markers was evaluated in samples obtained from in-vivo and in-vitro conditions with the help of RT-PCR and immunohistochemical staining analysis of OCT, SOX, Nestin, YAP and LATS-1 gene and protein expressions