PARP inhibitor olaparib sensitizes cholangiocarcinoma cells to radiation

Cancer Medicine
Yize MaoShengping Li

Abstract

Cholangiocarcinoma (CCA) is a highly malignant tumor with resistance to radiotherapy alone. Olaparib, a highly potent poly(ADP-ribose) polymerase (PARP) inhibitor, has been shown to sensitize many types of tumor to radiotherapy. However, the effect of olaparib, either as monotherapy or as combination therapy with radiotherapy, on CCA is not known, and our study aimed to explore this. To assess radiosensitization in three CCA cell lines (QBC939, HuH28 and TFK-1), viability and clonogenic assays were conducted. The absorbed radiation doses were 0 Gy, 2 Gy, 4 Gy, and 6 Gy; olaparib concentrations were 0 nmol/L, 1 nmol/L, 10 nmol/L, 100 nmol/L, 1000 nmol/L, 2500 nmol/L, 5000 nmol/L and 10 000 nmol/L. The mechanism of olaparib radiosensitization was explored by Western blotting. Immunofluorescence staining and flow cytometry were conducted to explore DNA damage and apoptosis. The radiosensitivity of CCA cells was enhanced by olaparib, which alone had little effect on the CCA cell lines without BRCA mutations. The degree of radiosensitization increased with increasing doses of olaparib by viability and clonogenic assays in vitro. Olaparib was able to enhance the effect of radiation by inhibiting PARP1, inducing DNA lesions and apopto...Continue Reading

References

Sep 19, 2002·Radiation Research·Olga A SedelnikovaWilliam M Bonner
Jul 27, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jean-Christophe AméGilbert de Murcia
Oct 11, 2005·Lancet·Shahid A KhanSimon D Taylor-Robinson
May 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeffrey M AlbertBo Lu
Mar 18, 2008·Current Opinion in Genetics & Development·Sarah A MartinAlan Ashworth
Jun 26, 2009·The New England Journal of Medicine·Peter C FongJohann S de Bono
Nov 27, 2009·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Yvette Drew, Ruth Plummer
Feb 20, 2010·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Marcel VerheijBaukelien van Triest
Nov 9, 2010·Journal of Hepatology·Côme LepageAnne-Marie Bouvier
Mar 25, 2011·Nature Reviews. Cancer·Adrian C BeggConchita Vens
Jun 8, 2011·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yu-Jie HouHong-Yang Wang
Oct 6, 2011·Molecular Cancer Therapeutics·Joana M SenraIan J Stratford
Jul 24, 2012·International Journal of Radiation Oncology, Biology, Physics·Ozlem U AtamanStephen R Wedge
Aug 17, 2012·Gut·Shahid A KhanUNKNOWN British Society of Gastroenterology
Mar 26, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S K SandhuJ de Bono
Oct 15, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Matthias PinterWolfgang Sieghart
Nov 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bella KaufmanSusan M Domchek
Jan 6, 2015·Chinese Journal of Cancer·Chiara Della PepaSando Pignata
May 13, 2015·Best Practice & Research. Clinical Gastroenterology·N Schweitzer, A Vogel
May 20, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Caroline V M VerhagenConchita Vens
Aug 11, 2015·Nature Genetics·Hiromi NakamuraTatsuhiro Shibata
Nov 29, 2016·Cancer Medicine·Erqi L PollomDaniel T Chang
Mar 18, 2017·Science·Christopher J Lord, Alan Ashworth

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Citations

Jan 21, 2020·Journal of Cellular and Molecular Medicine·Chuan LiuGuohua Hu
Jul 8, 2020·Cancers·Ana Beatriz VarandaRita Fior
Apr 19, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Colm J O'RourkeJesper B Andersen
Apr 24, 2021·Expert Review of Gastroenterology & Hepatology·Antonio CiglianoDiego F Calvisi
Aug 28, 2021·Biomedicines·Abdullah AlhusainiNiamh Lynam-Lennon

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Methods Mentioned

BETA
PCR
chip
AmpliSeq
irradiating
flow cytometry

Software Mentioned

Torrent Suite
SPSS
Ion Torrent Variant Caller
Ion OneTouch
Python
Ion Torrent

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