PT  - JOURNAL ARTICLE
AU  - KEISUKE MIYAMOTO
AU  - TETSUYA MINEGAKI
AU  - SAYAKA HIRANO
AU  - ITSUKA HAYASHI
AU  - MASAYUKI TSUJIMOTO
AU  - KOHSHI NISHIGUCHI
TI  - Olaparib Potentiates Anticancer Drug Cytotoxicity <em>via</em> 53BP1 in Oesophageal Squamous Cell Carcinoma Cells
AID  - 10.21873/anticanres.14013
DP  - 2020 Feb 01
TA  - Anticancer Research
PG  - 813--823
VI  - 40
IP  - 2
4099  - http://ar.iiarjournals.org/content/40/2/813.short
4100  - http://ar.iiarjournals.org/content/40/2/813.full
SO  - Anticancer Res2020 Feb 01; 40
AB  - Background/Aim: Olaparib was previously shown to synergistically enhance the cytotoxicity of DNA synthesis inhibitors in oesophageal carcinoma (OC) cell lines. However, the mechanisms of this synergy are not fully understood. As P53 binding protein 1 (53BP1) expression was previously shown to potentiate the anticancer effect of olaparib, we investigated the involvement of 53BP1 in the synergetic cytotoxic effects of olaparib and anticancer drugs in KYSE70 cells. Materials and Methods: Experiments included small interfering RNA transfection, growth inhibition assays, western blots, immunofluorescence, and flow cytometry. Results: The toxicity of DNA synthesis-inhibiting agents plus olaparib was decreased when 53BP1 was depleted. Olaparib cotreatment significantly increased phosphorylated H2A histone family member X (γH2AX) foci as well as 53BP1/γH2AX co-localisation in anticancer drug-treated cells. Silencing of 53BP1 suppressed anticancer drug-induced apoptosis with or without olaparib. Conclusion: Olaparib potentiates the cytotoxicity of anticancer drugs through 53BP1 in OC cells.