Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death

Ilaria Passacantilli, Valentina Panzeri, Francesca Terracciano, Gianfranco Delle Fave, Claudio Sette, Gabriele Capurso

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer and current treatments exert small effects on life expectancy. The most common adjuvant treatment for PDAC is gemcitabine. However, relapse almost invariably occurs and most patients develop metastatic, incurable disease. The aim of the present study was to assess the activity of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) alone or in combination with gemcitabine in PDAC cell lines displaying different degrees of sensitivity to gemcitabine treatment. We evaluated the effects of gemcitabine and nab-paclitaxel and their combination on cell proliferation, death, apoptosis and cell cycle distribution in PDAC cell lines either sensitive to gemcitabine, or with primary or secondary resistance to gemcitabine. Our results indicated that the dose‑response of PDAC cell lines to nab-paclitaxel was similar, regardless of their sensitivity to gemcitabine. In addition, nab-paclitaxel elicited similar cytotoxic effects on a PDAC cell line highly resistant to gemcitabine that was selected after prolonged exposure to the drug. Notably, we found that combined treatment with gemcitabine and nab-paclitaxel exerted additive effects on cell death, even at lower doses of the drugs. The combined treatment caused an increase in cell death by apoptosis and in cell cycle blockage in S phase, as assessed by flow cytometry and western blot analysis of the PARP-1 cleavage. These results revealed that a combined treatment with nab-paclitaxel may overcome resistance to gemcitabine and may represent a valuable therapeutic approach for PDAC.

Original languageEnglish
Pages (from-to)1984-1990
Number of pages7
JournalOncology Reports
Volume39
Issue number4
DOIs
Publication statusPublished - Apr 2018

Keywords

  • Adenocarcinoma/drug therapy
  • Albumins/pharmacology
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols/pharmacology
  • Apoptosis/drug effects
  • Carcinoma, Pancreatic Ductal/drug therapy
  • Cell Cycle/drug effects
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Deoxycytidine/adverse effects
  • Drug Resistance, Neoplasm/genetics
  • Gene Expression Regulation, Neoplastic/drug effects
  • Humans
  • Mice
  • Neoplasm Recurrence, Local/drug therapy
  • Paclitaxel/pharmacology
  • Poly (ADP-Ribose) Polymerase-1/genetics
  • Xenograft Model Antitumor Assays

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