PRIMA-1 increases cisplatin sensitivity in chemoresistant ovarian cancer cells with p53 mutation: a requirement for Akt down-regulation

Since ovarian cancer is associated with high frequency of p53 mutation, the availability of p53 reactivation and induction of massive apoptosis (PRIMA-1) offers a possible new therapeutic strategy for overcoming this devastating disease. Although Akt activation is believed to be a determinant in chemoresistance in ovarian cancer, whether Akt plays a role in regulating the effectiveness of PRIMA-1 in sensitizing chemoresistant ovarian cancer cells with p53 mutation to cisplatin (CDDP), remains to be determined. In the present studies, we examined the influence of Akt down-regulation following dominant-negative (DN-Akt) expression on the ability of PRIMA-1 (0-10 μM) to facilitate CDDP (0-10 μM)-induced apoptosis in p53-mutated chemoresistant ovarian cancer cells (A2780cp). Apoptosis rate was significantly higher at the combined treatment of low PRIMA-1 concentrations (0.156 - 0.938 μM) plus CDDP (10 μM) in the DN-Akt groups than control (p