Mar 30, 2020

Evaluating the Sensitivity of Sporadic Pancreatic Cancer to poly(ADP-ribose) polymerase (PARP) Inhibition (Velaparib, Olaparib, AG14361) as Single Agents and as Chemo-sensitizers

BioRxiv : the Preprint Server for Biology
Joseph Angel de Soto

Abstract

After resection of pancreatic cancer local recurrence occurs in 50% to 80% of the cases while metastasis develops 75% of the time. Current, adjuvant therapy often consists of gemcitabine, cisplatin and/or 5 fluorouracil which add a modest increase in median survival by 4-5 months. In this study, we treated human pancreatic cancer cells with poly (ADP-ribose) polymerase (PARP) Inhibitors (AG14361, Veliparib and Olaparib) alone or with gemcitabine, cisplatin or 5-fluorouracil. Methods: CFPAC-1 and BXPC-3, HPAC human pancreatic cancer cell lines were treated for 72 hours with PARP inhibitors alone or in combination with gemcitabine, cisplatin, or 5 fluorouracil. Validated MTT assays were used to form dose response curves from which the IC50 values were calculated. Results: The PARP1 IC50 values for CFPAC-1, BXPC-3 and HPAC pancreatic cancer cell lines were AG14361 (14.3, 12.7, 38.3 microM), Veliparib (52.6, 100.9, 102.0 microM) and Olaparib (79.5, 184.8, 200.2 microM). The IC50 values of cisplatin, were decreased up to 60 fold in the presence of clinically relevant amounts of PARP inhibitor while 5-flourouracil IC50 values were decreased up to 6000 fold in the presence of clinically relevant amounts of PARP inhibitor. Gemcitabine ...Continue Reading

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Mentioned in this Paper

Study
In Vivo
DNA Fragmentation
Abnormal Fragmented Structure
Genome
Genes
Malignant Neoplasm of Stomach
Enzymes, antithrombotic
Transcription, Genetic
Cosmids

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