BMC cancer
Characterization of etoposide-resistant choriocarcinoma cells and contribution of MAPK7 to etoposide resistance
By Yasui Y, Yoshida K, Nishiko Y and 12 others.
Abstract
Background
Gestational choriocarcinoma is an aggressive gynecologic malignancy that can occur with various pregnancy events. Although typically highly sensitive to combination chemotherapy, this malignancy, in a subset of patients, develops resistance to etoposide-containing regimens, leading to therapeutic failure. We aimed to elucidate the molecular mechanisms that confer resistance to etoposide, a central component of choriocarcinoma chemotherapy.
Methods
Etoposide-resistant JAR and JEG-3 choriocarcinoma cell lines were established by continuous stepwise exposure of parental cells to increasing concentrations of etoposide. Phenotypic comparisons with the parental cells were then performed. RNA sequencing and upstream regulator analyses were conducted to identify key regulatory molecules and signaling pathways associated with etoposide resistance. Candidate molecules were further evaluated by siRNA-mediated knockdown to assess their effects on etoposide sensitivity.