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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

Olaparib delayed the growth of the JF-305 tumors in vivo compared with the vehicle. RTV, relative tumor volume; ip, intraperitoneal injection; qd, once daily. Results are presented as the mean ± standard deviation (n=6).
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f4-ol-09-02-0757: Olaparib delayed the growth of the JF-305 tumors in vivo compared with the vehicle. RTV, relative tumor volume; ip, intraperitoneal injection; qd, once daily. Results are presented as the mean ± standard deviation (n=6).

Mentions: The results from the present study demonstrated that the JF-305 cells were sensitive to olaparib in vitro. In addition, JF-305 cells have also previously been reported to exhibit tumorigenicity when transplanted into nude mice (16). In the present study, upon assessment of the response of JF-305 tumors to olaparib in vivo, tumor formation was detected after two weeks of inoculation. The mean tumor volume in the control group increased to 1,368 mm3 by the 5th week, and to 687 mm3 in the olaparib-treated group (P<0.05), a 49.8% reduction following 22 consecutive days of administration (Fig. 4).


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)

Olaparib delayed the growth of the JF-305 tumors in vivo compared with the vehicle. RTV, relative tumor volume; ip, intraperitoneal injection; qd, once daily. Results are presented as the mean ± standard deviation (n=6).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-ol-09-02-0757: Olaparib delayed the growth of the JF-305 tumors in vivo compared with the vehicle. RTV, relative tumor volume; ip, intraperitoneal injection; qd, once daily. Results are presented as the mean ± standard deviation (n=6).
Mentions: The results from the present study demonstrated that the JF-305 cells were sensitive to olaparib in vitro. In addition, JF-305 cells have also previously been reported to exhibit tumorigenicity when transplanted into nude mice (16). In the present study, upon assessment of the response of JF-305 tumors to olaparib in vivo, tumor formation was detected after two weeks of inoculation. The mean tumor volume in the control group increased to 1,368 mm3 by the 5th week, and to 687 mm3 in the olaparib-treated group (P<0.05), a 49.8% reduction following 22 consecutive days of administration (Fig. 4).

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