JF-305, a pancreatic cancer cell line is highly sensitive to the PARP inhibitor olaparib

Yang,Xueli; Ndawula ,Charles; Zhou,Haiyan; Gong,Xiaohai; Jin,Jian

doi:10.3892/ol.2014.2762

JF-305, a pancreatic cancer cell line is highly sensitive to the PARP inhibitor olaparib

Authors:
- Xueli Yang
- Charles Ndawula
- Haiyan Zhou
- Xiaohai Gong
- Jian Jin
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Affiliations: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China, National Livestock Resources Research Institute, Tororo, Uganda
Published online on: December 3, 2014 https://doi.org/10.3892/ol.2014.2762
Pages: 757-761

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Abstract

Poly(ADP‑ribose) polymerase‑1 (PARP‑1) is a DNA nick sensor involved in the base excision repair (BER) pathway. Olaparib, a PARP inhibitor, has demonstrated antitumor activity in homologous recombination (HR)‑deficient cancers. To extend this specific therapy to other types of carcinomas, a panel of 11 different cancer cells were screened in the present study. JF‑305, a pancreatic cancer cell line of Chinese origin, demonstrated sensitivity to the PARP inhibitor 6(5H)‑phenanthridinone. In the present study, 3 µM olaparib conferred a cell survival rate of 25% following four days of treatment. The colony formation efficiency was 83% at 10 nM, and dropped to 12% at 1 µM following seven days of treatment. Furthermore, olaparib induced cell cycle arrest in the S and G2/M phases prior to the initiation of apoptosis. Although the incidence of double‑strand breaks (DSBs) was increased in the olaparib‑treated JF-305 cells, the RAD51 foci were well formed at the sites of γ‑H2AX recruitment, indicating an activated HR mechanism. Furthermore, tumor growth was reduced by 49.8% following 22 days of consecutive administration of 10 mg/kg olaparib in the JF‑305 xenograft mouse model. In summary, the JF‑305 cell line was sensitive to olaparib and provided a prospective model for the preclinical assessment of PARP inhibitors in the therapy of pancreatic cancer.

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