Figure 5. Pyrvinium pamoate enhances DNA double-strand breaks in vitro and in vivo.

(A) Pyrvinium pamoate enhances doxorubicin-induced DNA double-strand breaks in 5637 cells as indicated by increased γH2AX levels. (B) AMPK or Cdk1 inhibition weakens pyrvinium pamoate-mediated increase of γH2AX levels during doxorubicin's treatment. Immunofluorescence assay were conducted for γH2AX staining (magnification, 100×). Left, representative images; right, quantification of γH2AX foci. (C) Pyrvinium pamoate strengthens DNA double-strand breaks in an alkaline comet assay. H₂O₂ at concentration of 200 μmol/L was used as a positive control. Average tail moments were measured from 50 comet tails of each group. Columns, mean; bars, standard deviation. (D) Pyrvinium pamoate reverses cisplatin-triggered HuR cytoplasmic accumulation in tumors from the primary bladder tumor xenograft mouse model (UCBPDX0615). Representative images were shown (magnification, 20×). (E) Addition of pyrvinium pamoate leads to a significantly higher level of γH2AX in tumor tissues. Percentage of γH2AX positive cells in tumors from xenograft mouse model (UCBPDX0615) was shown. Columns, mean; error bars, standard deviation. *P < 0.05; **P < 0.01; ***P < 0.001. CDDP, cisplatin; Dox, doxorubicin; PP, pyrvinium pamoate; CC, compound C; AZD, AZD5438.