Radiotherapy combined with gemcitabine and oxaliplatin in pancreatic cancer cells

Meredith A. Morgan, Amichay Meirovitz, Mary A. Davis, Laura E. Kollar, Maria C. Hassan, Theodore S. Lawrence

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Clinical evidence suggests that gemcitabine (Gem) plus oxaliplatin (Ox) is superior to gemcitabine alone in advanced pancreatic carcinoma. The addition of radiation to gemcitabine improves response and is a standard treatment for locally advanced disease. We investigated the effect of oxaliplatin on gemcitabine-based chemoradiation by determining whether gemcitabine and oxaliplatin produced synergistic cytotoxicity using median effect analysis and radiosensitization using clonogenic survival assays. We analyzed the effects of gemcitabine and oxaliplatin on cell cycle distribution by DNA content and on radiation-induced DNA damage repair by phosphorylated H2AX (γ-H2AX). Gemcitabine and oxaliplatin produced schedule-dependent synergistic cytotoxicity in BxPC-3 and Panc-1 cells (combination indices: 0.76 ± 0.05, 0.61 ± 0.11). In BxPC-3 cells, oxaliplatin did not affect gemcitabine-mediated radiosensitization (Gem 1.99 ± 0.27; Gem + Ox 2.38 ± 0.30). In Panc-1 cells, oxaliplatin significantly enhanced gemcitabine-mediated radiosensitization (Gem 1.31±0.05; Gem+Ox 2.90±0.31). Radiosensitization by gemcitabine was accompanied by early S-phase arrest and induction/persistence of γ-H2AX protein, which were unaltered by oxaliplatin. Addition of oxaliplatin to gemcitabine produces radiosensitization equal to or greater than gemcitabine alone, supporting our clinical investigation of oxaliplatin with gemcitabine-radiation in pancreatic cancer aimed at improving systemic disease control while maintaining local tumor radiosensitization.

Original languageEnglish
Pages (from-to)36-43
Number of pages8
JournalTranslational Oncology
Volume1
Issue number1
DOIs
StatePublished - 1 Jan 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Radiotherapy combined with gemcitabine and oxaliplatin in pancreatic cancer cells'. Together they form a unique fingerprint.

Cite this