Trichostatin A enhances the response of chemotherapeutic agents in inhibiting pancreatic cancer cell proliferation.
Pancreatic cancer is an aggressive neoplasia, and standard chemotherapies are by and large ineffective. The purpose of this work was to get a comprehensive preclinical study on the ability of anticancer drug combinations that best inhibit growth of pancreatic adenocarcinoma cells. We evaluated the in vitro growth inhibition of ten pancreatic cancer cell lines to gemcitabine and 5-fluorouracil, newer generation cytotoxic agents (oxaliplatin, irinotecan), targeted therapy (gefitinib) and a histone deacetylase (HDAC) inhibitor (trichostatin A). Cells were treated with the single drug alone and all pairwise drug association. Our results demonstrate that TSA can effectively increase the drug sensitivity of all the cell lines studied. The association of TSA and irinotecan determines an increase in growth inhibition on the highest percentage of cell lines (80%). Our findings may represent an experimental basis for potential clinical application of HDAC inhibitors, in particular in association with drugs used in cancer clinical treatment, supporting the idea that HDAC inhibitors could act as sensitizers for chemotherapy.
Piacentini
Paolo
P
Department of Pathology, Section of Anatomic Pathology, University of Verona, Verona, Italy.
Donadelli
Massimo
M
Costanzo
Chiara
C
Moore
Patrick S
PS
Palmieri
Marta
M
Scarpa
Aldo
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; C012589:trichostatin A; D000077146:Irinotecan; D002166:Camptothecin