Targeting the CtBP1-FOXM1 transcriptional complex with small molecules to overcome MDR1-mediated chemoresistance in osteosarcoma cancer stem cells.

ABSTRACT: Chemoresistance is a major barrier for the chemotherapy of osteosarcoma. The induction of multidrug resistance protein 1 (MDR1), an ATP-dependent transporter, can efflux anti-cancer drugs, thereby decreasing chemosensitivity. However, an actual involvement of MDR1 in the chemoresistance of osteosarcoma cells has not been established. We obtained two cisplatin (CDDP)-resistant osteosarcoma cancer stem cell (CSC) lines using sphere formation medium supplemented with CDDP. These two CDDP-resistant CSC cell lines showed substantial cell proliferation, colony formation, cell invasion, and in vivo tumor growth in the presence of CDDP. Microarray analysis revealed that three genes, MDR1, FOXM1 (forkhead box M1), and CtBP1 (C-Terminal binding protein 1), showed signific

SUBMITTER: Chen X 

PROVIDER: S-EPMC7739006 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature