Synergistic Effect of Trabectedin and Olaparib Combination Regimen in Breast Cancer Cell Lines

Journal of breast cancer
Sonia Ávila-ArroyoCarlos M Galmarini

Abstract

Trabectedin induces synthetic lethality in tumor cells carrying defects in homologous recombinant DNA repair. We evaluated the effect of concomitant inhibition of nucleotide-excision repair and poly (ADP-ribose) polymerase (PARP) activity with trabectedin and PARP inhibitors, respectively, and whether the synthetic lethality effect had the potential for a synergistic effect in breast cancer cell lines. Additionally, we investigated if this approach remained effective in BRCA1-positive breast tumor cells. We have evaluated the in vitro synergistic effect of combinations of trabectedin and three different PARP inhibitors (veliparib, olaparib, and iniparib) in four breast cancer cell lines, each presenting a different BRCA1 genetic background. Antiproliferative activity, DNA damage, cell cycle perturbations and poly(ADP-ribosyl)ation were assessed by MTT assay, comet assay, flow cytometry and western blot, respectively. The combination of trabectedin and olaparib was synergistic in all the breast cancer cell lines tested. Our data indicated that the synergy persisted regardless of the BRCA1 status of the tumor cells. Combination treatment was associated with a strong accumulation of double-stranded DNA breaks, G2/M arrest, and apo...Continue Reading

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Citations

Aug 25, 2016·Hereditary Cancer in Clinical Practice·Aglaya G Iyevleva, Evgeny N Imyanitov
Oct 25, 2016·Cancer Treatment Reviews·Bradley J MonkMaurizio D'Incalci
Nov 4, 2016·Expert Opinion on Investigational Drugs·M TampelliniG V Scagliotti
Apr 21, 2017·Expert Review of Anticancer Therapy·E SkafidaA Digklia
Jan 21, 2017·Journal of Cellular Biochemistry·Muhammad TariqBo Yang
Apr 13, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·S TaoY Ding
Apr 13, 2017·Journal of Hematology & Oncology·Audrey LarocheAntoine Italiano
May 23, 2018·Journal of Experimental & Clinical Cancer Research : CR·Hye Jeong ParkKyu Yun Jang
Dec 14, 2018·Carcinogenesis·Laura CarminatiGiulia Taraboletti
Jul 26, 2019·The Breast : Official Journal of the European Society of Mastology·Shani Paluch-Shimon, Ella Evron

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Methods Mentioned

BETA
electrophoresis
PARylation

Software Mentioned

Prism
CometScore
CalcuSyn
Modfit LT

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