cancer-research-structural-biochemistry-2019-posters

Page 59

Volume 3

August 5-6, 2019 | Singapore

CANCER RESEARCH AND PHARMACOLOGY

STRUCTURAL BIOCHEMISTRY, STEM CELLS AND MOLECULAR BIOLOGY

International Conference on

International Congress on

Cancer Research 2019 & Structural Biochemistry 2019

August 5-6, 2019

Journal of Cancer and Metastasis Research

Clin Psychol Cog Sci, Volume 3

Combination of bortezomib with olaparib decreases ovarian cancer chemoresistance

Caglar Berkel

Tokat Gaziosmanpasa University, Turkey

Statement of the Problem

: Ovarian cancer is one of the deadliest

malignancies in women and chemoresistance is a challenge for

management of ovarian cancer. In this study, we aimed to investigate

the cytotoxic efficacy of combination treatment with bortezomib

(inhibition of 26S proteasome) and olaparib (inhibition of poly

(ADP- ribose) polymerases (PARP); PARPi) on chemosensitive and

chemoresistant ovarian cancer cell lines. Methodology & Theoretical

Orientation: Experiments were performed in both chemosensitive

ovarian cancer cell lines (OV2008, A2780) and their chemoresistant

daughter cell lines (C13, A2780-AD). Cell viability was evaluated

by Sulphorhodamine B (SRB) assay following bortezomib and/or

olaparib treatments with or without cisplatin.

Findings

: Bortezomib and olaparib combination treatment resulted

in increased cytotoxicity relative to either drug alone at certain

concentrations in both chemosensitive and chemoresistant ovarian

cancer cell lines. In addition, combination treatment sensitized these

tumor cells to cisplatin and decreased chemoresistance at certain

concentrations used.

Conclusion & Significance

: This study suggests that combination of proteasome inhibition with PARP inhibition shows

increased efficacy when compared to use of either drug alone in ovarian cancer cells. Based on this preclinical study, it can

be assumed that administration of these agents in combination (bortezomib plus olaparib) to ovarian cancer patients may exert

enhanced therapeutic effects in the clinic, improving the effect of either drug alone.

Figure 1. Representative figure of cytotoxicity of bortezomib (B) plus olaparib

treatment for one of the ovarian cancer cell lines used in this study (OV2008). In this

particularcell line,atB10+O10andB20+O20,cellviabilitydecreasessignificantly

when compared to effects of either drug alone. B: bortezomib, O: olaparib.