Abstract

Neuroblastoma is the most common type of cancer diagnosed in children aged between one and five years old. Diagnosed children with high-risk neuroblastoma have a 5-year survival rate of approximately 50%. Cisplatin is a commonly used treatment for high-risk neuroblastoma, unfortunately, it is often challenged with chemoresistance due to the induction of autophagy. Autophagy is an interesting cellular pathway that is considered a double-edged sword; it can either enhance apoptosis and suppress tumor progression or promote cell survival thus promoting tumorigenesis.

The current study aimed to explore the role of autophagy inhibition as an adjuvant to chemotherapy on neuroblastoma SK-N-AS cells in vitro. Bafilomycin A-1; 200 nM, was used either as a pretreatment or concurrently with Cisplatin. Cell viability assessment showed that pretreatment with Bafilomycin A1 significantly enhanced cell death of SK-N-AS cells induced by Cisplatin with 82% decrease in cell viability compared to only a 31% decrease with Cisplatin alone. Cell death was further confirmed with flow cytometric analysis of apoptosis, confirming that Bafilomycin A1 pretreatment resulted in a higher percentage of apoptotic cells and induced a G0-G1 phase cell cycle arrest. Furthermore, Bafilomycin A1 pretreatment downregulated mRNA expression of pivotal genes such as ATG7, implying that inhibiting autophagic flux sensitizes neuroblastoma cells to Cisplatin. Additionally, Bafilomycin A1 pretreatment significantly downregulated MYCN, a key chemoresistance driver in high-risk neuroblastoma.

In conclusion, the current findings highlight the use of Bafilomycin A-1 as an adjuvant treatment with chemotherapy as a promising treatment strategy to overcome autophagy-mediated chemoresistance in high-risk neuroblastoma and improve treatment outcomes in pediatric cancer patients.

School

School of Sciences and Engineering

Department

Biotechnology Program

Degree Name

MS in Biotechnology

Graduation Date

Winter 2-19-2025

Submission Date

1-28-2025

First Advisor

Ahmed Abdellatif

Committee Member 1

Andreas Kakarougkas

Committee Member 2

Nivin Shaarawy

Committee Member 3

Walid Fouad

Extent

64 p.

Document Type

Master's Thesis

Institutional Review Board (IRB) Approval

Not necessary for this item

Download

Available for download on Thursday, January 28, 2027

Share

COinS