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Type: Theses
Title: Investigation of novel therapeutic strategies for epithelial ovarian cancer
Author: Yoshikawa, Nobuhisa
Issue Date: 2016
School/Discipline: School of Medicine
Abstract: Objective: PRIMA-1MET is a small molecule compound that restores wild-type p53 to mutant p53, and is recently confirmed to be safe at therapeutic plasma levels. The aims of this study were to identify the anti-tumour activity of PRIMA-1MET on epithelial ovarian cancer (EOC) cells and elucidate the underlying mechanism in vitro. Methods: We used nine EOC cell lines and their chronic cisplatin/paclitaxel-resistant cells and performed cell viability assay and cell apoptosis assay to evaluate the efficacy of PRIMA-1MET. Moreover, we assessed the functional role of reactive oxygen species (ROS) and their scavenger in the EOC cells. Results: We examined the viability of the total 13 EOC cells after 48 h treatment with PRIMA-1MET. Measuring the half maximal inhibitory concentration (IC₅₀) of EOC cells revealed that the sensitivity was heterogeneous, and did not correlate with TP53 status. PRIMA-1MET induced apoptosis, PARP cleavage, and intracellular ROS accumulation in a p53-independent manner. The anti-tumour effects of PRIMA-1MET were completely rescued by a ROS scavenger, N-acetyl cysteine. Furthermore, PRIMA-1MET reduced the expression of antioxidant enzymes, PRX3 and GPX1, in a dose-dependent manner. Conclusion: We demonstrated that PRIMA-1MET had an anti-tumour effect on EOC cells regardless of TP53 status and chemo-resistance. PRIMA-1MET is a promising therapeutic agent for chemo-resistant EOC patients and may contribute to a better prognosis in the future.
Advisor: Callen, David Frederick
Kikkawa, Fumitaka
Pishas, Kathleen
Worthley, Daniel
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2016.
Keywords: ovarian cancer
antioxidant enzyme
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
Appears in Collections:Research Theses

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