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

Yang X, Ndawula C, Zhou H, Gong X, Jin J - Oncol Lett (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus

Compared with other cell types, JF-305 cells demonstrate relatively high sensitivity of their colony formation efficiency to the PARP inhibitor PHE. Rin5f, islet tumor cell; B16, skin melanoma cell; Acc-3, salivary gland adenoid cystic carcinoma cell; Patu8988, pancreatic cancer cell; Bel7402, hematoma cell; HNE2, nasopharyngeal carcinoma cell; HepG2, hepatocellular carcinoma cell; DU145, prostate cancer cell; SGC7901, gastric cancer cell; A549, lung adenocarcinoma cell; PHE, 6(5H)-phenanthridinone. Data are expressed as the mean ± standard deviation (n=3).
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f1-ol-09-02-0757: Compared with other cell types, JF-305 cells demonstrate relatively high sensitivity of their colony formation efficiency to the PARP inhibitor PHE. Rin5f, islet tumor cell; B16, skin melanoma cell; Acc-3, salivary gland adenoid cystic carcinoma cell; Patu8988, pancreatic cancer cell; Bel7402, hematoma cell; HNE2, nasopharyngeal carcinoma cell; HepG2, hepatocellular carcinoma cell; DU145, prostate cancer cell; SGC7901, gastric cancer cell; A549, lung adenocarcinoma cell; PHE, 6(5H)-phenanthridinone. Data are expressed as the mean ± standard deviation (n=3).

Mentions: In the present study, the effects of the PARP inhibitor, PHE (IC50, 350 nM) (13), on the colony formation efficiency of various cell lines was investigated. The pancreatic cancer JF-305 cell line was identified to be the most sensitive to PHE, as its colony formation efficiency decreased to <10% when treated with 10 μM PHE, a concentration at which other cell lines retained at least 60% colony formation efficiency (P<0.05) (Fig. 1).


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

Yang X, Ndawula C, Zhou H, Gong X, Jin J - Oncol Lett (2014)

Compared with other cell types, JF-305 cells demonstrate relatively high sensitivity of their colony formation efficiency to the PARP inhibitor PHE. Rin5f, islet tumor cell; B16, skin melanoma cell; Acc-3, salivary gland adenoid cystic carcinoma cell; Patu8988, pancreatic cancer cell; Bel7402, hematoma cell; HNE2, nasopharyngeal carcinoma cell; HepG2, hepatocellular carcinoma cell; DU145, prostate cancer cell; SGC7901, gastric cancer cell; A549, lung adenocarcinoma cell; PHE, 6(5H)-phenanthridinone. Data are expressed as the mean ± standard deviation (n=3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4301471&req=5

f1-ol-09-02-0757: Compared with other cell types, JF-305 cells demonstrate relatively high sensitivity of their colony formation efficiency to the PARP inhibitor PHE. Rin5f, islet tumor cell; B16, skin melanoma cell; Acc-3, salivary gland adenoid cystic carcinoma cell; Patu8988, pancreatic cancer cell; Bel7402, hematoma cell; HNE2, nasopharyngeal carcinoma cell; HepG2, hepatocellular carcinoma cell; DU145, prostate cancer cell; SGC7901, gastric cancer cell; A549, lung adenocarcinoma cell; PHE, 6(5H)-phenanthridinone. Data are expressed as the mean ± standard deviation (n=3).
Mentions: In the present study, the effects of the PARP inhibitor, PHE (IC50, 350 nM) (13), on the colony formation efficiency of various cell lines was investigated. The pancreatic cancer JF-305 cell line was identified to be the most sensitive to PHE, as its colony formation efficiency decreased to <10% when treated with 10 μM PHE, a concentration at which other cell lines retained at least 60% colony formation efficiency (P<0.05) (Fig. 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus