Transcriptomic changes upon doxorubicin treatment in hCMEC/D3

Current chemotherapy regimens have significantly improved overall survival for children with cancer. However, these curative treatments are associated with detrimental side effects such as chemotherapy-induced cognitive impairment (CICI), or “chemobrain.” Measurable deficits in cognitive function may persist years after chemotherapy treatments, significantly reducing quality of life. Specifically, doxorubicin (DOXO), a commonly used chemotherapeutic agent in curative regimens for children with cancer, plays a pivotal role in the development of CICI, even though it does not cross the blood brain barrier (BBB). We propose to address the poorly understood mechanism of DOXO-related CICI by studying changes induced by DOXO in BBB integrity in vitro, using human cerebral microvascular endothelial cells (hCMEC/D3). Our findings provide critical insights on how DOXO impacts the BBB and builds a foundation for developing preventative measures and therapeutic interventions that may improve the quality of life for patients. Overall design: RNA-sequencing was performed to gain insights regarding the gene expression changes induced by doxorubicin (DOXO) treatment in human cerebral microvascular endothelial cells (hCMEC/D3). The hCMEC/D3 were treated 500 nM of doxorubicin (DOXO) or PBS, for 24 hours.