Effects of Poly (ADP-ribosyl) Polymerase (PARP) Inhibitor on Cisplatin Resistance & Proliferation of the Ovarian Cancer C13* Cells

Overview

Journal Indian J Med Res

Specialty General Medicine

Date 2013 May 4

PMID 23640560

Citations 9

Authors

Jingjing Zhang

Yanyan Kan

Yongjie Tian

Zhe Wang

Jie Zhang

Affiliations

Soon will be listed here.

Abstract

Background & Objectives: Drug resistance is the primary cause of failure in the treatment of cancers. It has been suggested that the enhancement of DNA repair capability may be responsible for the drug resistance of the tumour cells, and poly(ADP-ribosyl)ation plays an important role in DNA repair. This study investigated the effect of PARP inhibitor 3-aminobenzamide (3-AB) on the cisplatin resistance and proliferation of the cisplatin-resistant ovarian cancer C13 FNx01 cells in vitro.

Methods: C13 FNx01 cells were treated with various concentrations of 3-AB in vitro. MTT assay was used to determine the effect of 3-AB on the cisplatin sensitivity and proliferation of cells. The expression levels of PARP-1 mRNA and protein in the C13 FNx01 cells were examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and changes caused by 3-AB treatment were investigated. Immunofluorescence microscopy was used to detect the localization and expression of the PARP-1 proteins before and after treatment with 5 mmol/l 3-AB.

Results: The inhibitory ratio and the cisplatin sensitivity of C13 FNx01 cells significantly increased with the increase of the concentration of 3-AB (P<0.05). The RT-PCR analysis revealed that the expression of PARP-1 mRNA was decreased when platinum (Pt) and 3-AB were combined. The expression levels of PARP-1 protein were decreased by 23.15 ± 2.53, 59.11 ± 2.23 and 73.24 ± 3.88 per cent, respectively, in C13 FNx01 cells with the increase of the concentration of 3-AB (P<0.05). The immunofluorescence microscopy results indicated that the expression level of PARP-1 protein was significantly decreased after treatment with 3-AB (P,<0.05).

Interpretation & Conclusions: 3-AB inhibited the proliferation activity of C13 FNx01 cells, and increased the cellular sensitivity to cisplatin. Our findings show that the PARP inhibitor 3-AB can downregulate the expression of PARP-1 at transcriptional and translational levels in C13 FNx01 cells.

Citing Articles

The emerging role of circular RNAs in cisplatin resistance in ovarian cancer: From molecular mechanism to future potential.

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Ovarian cancer resistance to PARPi and platinum-containing chemotherapy.

Summey R, Uyar D Cancer Drug Resist. 2022; 5(3):637-646.

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Hsa_circ_0063804 enhances ovarian cancer cells proliferation and resistance to cisplatin by targeting miR-1276/CLU axis.

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Unsymmetric Cisplatin-Based Pt(IV) Conjugates Containing a PARP-1 Inhibitor Pharmacophore Tested on Malignant Pleural Mesothelioma Cell Lines.

Gabano E, Pinton G, Balzano C, Boumya S, Osella D, Moro L Molecules. 2021; 26(16).

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Potential role of HGF-PARP-1 signaling in invasion of ovarian cancer cells.

Wei W, Lv S, Zhang C, Tian Y Int J Clin Exp Pathol. 2020; 11(7):3310-3317.

PMID: 31949706 PMC: 6962858.

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