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Journal of Ovarian Research

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Open Access 01-12-2013 | Research

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

Authors: Noriko Kobayashi, Mohammadreza Abedini, Noriaki Sakuragi, Benjamin K Tsang

Published in: Journal of Ovarian Research | Issue 1/2013

Abstract

Background

Since ovarian cancer is associated with high frequency of p53 mutation, the availability of p 53 r eactivation and i nduction of m assive a poptosis (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.

Methods

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).

Results

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<0.001). Apoptosis in cells treated with PRIMA-1 (0.156 μM) and CDDP treatment (10 μM) was significantly suppressed by p53-siRNA. PRIMA-1 increased phospho-p53 (Ser15) content in Akt down-regulated cells treated with CDDP.

Conclusions

These results demonstrate that PRIMA-1 can sensitize chemoresistant ovarian cancer cells with p53 mutation to CDDP when Akt is down-regulated, and the action of PRIMA-1 is associated with p53 activation. Our findings raise the possibility that PRIMA-1 may be useful candidate for adjuvant therapy with CDDP in chemoresistant ovarian cancer with p53 mutation when Akt is down-regulated.

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Title: PRIMA-1 increases cisplatin sensitivity in chemoresistant ovarian cancer cells with p53 mutation: a requirement for Akt down-regulation
Authors: Noriko Kobayashi
Mohammadreza Abedini
Noriaki Sakuragi
Benjamin K Tsang
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/1757-2215-6-7

ACC 2024 Congress

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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