(A) Pyrvinium pamoate dose-dependently inhibits doxorubicin-induced overexpression of BRCA2, LIG4 and RAD51 genes. The relative changes in gene expression were expressed using untreated cells at 100%. (B) Pyrvinium pamoate decreases mRNA stability of BRCA2, LIG4 and RAD51 genes. (C) Pyrvinium pamoate decreases LIG4 protein level in a dose-dependent manner. Upper, LIG4 expression; lower, decreased LIG4 expression by pyrvinium pamoate. (D) Pyrvinium pamoate inhibits doxorubicin-induced HuR binding to LIG4 3′UTR. 5637 cells were transiently transfected with either empty vector pLuc reporter plasmid or a 3′UTR reporter construct. Dots or Columns, mean of four independent replicates; bars, standard deviation. Dox, doxorubicin; PP, pyrvinium pamoate; wt, wild-type; K.O., knockout. (E) Schematic diagram of pyrvinium pamoate in potentiating chemotherapeutic efficacy. Grey proteins refer to inactive state and red ones refer to active state.