Terfenadine resensitizes doxorubicin activity in drug-resistant ovarian cancer cells via an inhibition of CaMKII/CREB1 mediated ABCB1 expression.

ABSTRACT: Ovarian cancer is one of the most lethal gynecological malignancies. Recurrence or acquired chemoresistance is the leading cause of ovarian cancer therapy failure. Overexpression of ATP-binding cassette subfamily B member 1 (ABCB1), commonly known as P-glycoprotein, correlates closely with multidrug resistance (MDR). However, the mechanism underlying aberrant ABCB1 expression remains unknown. Using a quantitative high-throughput combinational screen, we identified that terfenadine restored doxorubicin sensitivity in an MDR ovarian cancer cell line. In addition, RNA-seq data revealed that the Ca2+-mediated signaling pathway in the MDR cells was abnormally regulated. Moreover, our research demonstrated that terfenadine directly bound to CAMKIID to prevent its autophosphorylation and inhibit

SUBMITTER: Huang W 

PROVIDER: S-EPMC9684669 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature