Synergistic effects of olaparib combined with <em>ERCC1</em> on the sensitivity of cisplatin in non‑small cell lung cancer

Xie,Kejie; Ni,Xiaoyan; Lv,Shanmei; Zhou,Guozhong; He,Honger

doi:10.3892/ol.2021.12626

Synergistic effects of olaparib combined with ERCC1 on the sensitivity of cisplatin in non‑small cell lung cancer

Authors:
- Kejie Xie
- Xiaoyan Ni
- Shanmei Lv
- Guozhong Zhou
- Honger He
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Affiliations: Department of Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China, Department of Radiotherapy, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China
Published online on: March 10, 2021 https://doi.org/10.3892/ol.2021.12626
Article Number: 365
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non‑small cell lung cancer (NSCLC) is a common malignant tumor. ERCC excision repair 1 endonuclease non‑catalytic subunit (ERCC1) is a key mediator of nucleotide excision repair. The present study aimed to explore the synergistic effects of the poly(ADP‑ribose) polymerase (PARP) inhibitor olaparib combined with ERCC1 on the sensitivity of NSCLC cells to cisplatin. Preliminary experiments were performed to identify the optimal concentrations of cisplatin and olaparib for cellular treatment and subsequently NCI‑H1299 and SK‑MES‑1 cells were treated with 20 µg/ml cisplatin combined with 50 µg/ml olaparib and 50 µg/ml cisplatin combined with 70 µg/ml olaparib, respectively. Subsequently, transfections were carried out to overexpress or knockdown the expression of ERCC1 in NSCLC cell lines, including NCI‑H1299 and SK‑MES‑1. The transfection efficiency was evaluated using reverse transcription‑quantitative PCR and western blotting. The results demonstrated that cells with ERCC1 overexpression and ERCC1 knockdown were successfully constructed. Finally, the cell viability and apoptosis were determined using the Cell Counting Kit‑8 and Annexin V‑FITC cell apoptosis assays, respectively. In NCI‑H1299 or SK‑MES‑1 cells treated with cisplatin combined with olaparib for 24 h, the cell viability significantly increased following ERCC1 overexpression compared with the GV230 group (P<0.05), but significantly inhibited following ERCC1 knockdown compared with the siRNA‑NC group (P<0.05). However, ERCC1 overexpression or knockdown had the opposite effect on apoptosis. In conclusion, olaparib combined with ERCC1 expression may enhance the sensitivity of cisplatin in NSCLC. These findings may provide novel insight for the improvement of platinum drug sensitivity and treatment of NSCLC.

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