Interplay Between Gemcitabine and Erlotinib Over Pancreatic Adenocarcinoma Cells

• Published in: Pancreas Vol. 45; no. 2; p. 269
• Main Authors: Torres, Carolina, Linares, Ana, Alejandre, Maria Jose, Palomino-Morales, Rogelio Jesus, Delgado, Juan Ramon, Perales, Sonia
• Format: Journal Article
• Language: English
• Published: United States 01.02.2016
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Apoptosis - genetics; Blotting, Western; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cell Survival - drug effects; Cell Survival - genetics; Cyclin-Dependent Kinase Inhibitor p27 - genetics; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Drug Interactions; Erlotinib Hydrochloride - pharmacology; G1 Phase Cell Cycle Checkpoints - drug effects; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression Regulation, Neoplastic - drug effects; Humans; NF-kappa B - genetics; NF-kappa B - metabolism; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Signal Transduction - genetics
• ISSN: 1536-4828
• DOI: 10.1097/MPA.0000000000000452

Pancreatic ductal adenocarcinoma remains as a chemoresistant disease with the poorest prognosis. Gemcitabine has been the standard treatment during the last decade. Erlotinib, a tyrosine kinase inhibitor, in combination with gemcitabine produces a small increase in survival. However, these results remain insufficient. The aim of this study was to investigate the molecular interplay in vitro between them regarding their effects over cytotoxicity, proliferation, apoptosis, and invasion. Using the human pancreatic cancer cell lines Panc-1 and BxPC-3 in vitro, the effects of gemcitabine and erlotinib therapy on growth, proliferation, and invasion were tested by cytotoxicity, cell cycle, and Annexin V-Fluorescein Isothiocyanate analysis, reverse transcription polymerase chain reaction, protein expression, and Chip assays. Therapy decreased cell proliferation causing G0/G1 phase cell cycle arrest with induction of apoptosis in the Panc-1 cell line. This blockade was associated with increased p27 expression. Besides, treatments enhanced the nuclear factor-κB (NF-κB) pathway and the binding of NF-κB to the promoters of genes related to the proliferation and the evasion of apoptosis. Our data suggest that, although gemcitabine and erlotinib exert antiproliferative effects over pancreatic cancer cell lines, the gemcitabine-induced activation of NF-κB expression and its DNA-binding activities are important drawbacks of this treatment against pancreatic cancer.