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

doi:10.1593/tlo.07106

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 journal › Article › peer-review

22 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 language	English
Pages (from-to)	36-43
Number of pages	8
Journal	Translational Oncology
Volume	1
Issue number	1
DOIs	https://doi.org/10.1593/tlo.07106
State	Published - 1 Jan 2008
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1593/tlo.07106

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@article{8af0c023e12c45098cb856dc2328ecc0,

title = "Radiotherapy combined with gemcitabine and oxaliplatin in pancreatic cancer cells",

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.",

author = "Morgan, {Meredith A.} and Amichay Meirovitz and Davis, {Mary A.} and Kollar, {Laura E.} and Hassan, {Maria C.} and Lawrence, {Theodore S.}",

note = "Funding Information: Address all correspondence to: Meredith A. Morgan, PhD, Department of Radiation Oncology, University of Michigan Medical Center, 1331 East Ann Street, Room 3111 East Ann Building, Ann Arbor, MI 48109-5582, USA. E-mail: [email protected] 1This work was supported by grant no. CA78554 and by the University of Michigan Cancer Center support grant no. 5 P30 CA46592. 2These authors contributed equally to this work. Received 10 July 2007; Revised 1 October 2007; Accepted 5 October 2007 Copyright {\textcopyright} 2008 Neoplasia Press, Inc. Open access under CC BY-NC-ND license. 1522-8002/08/$25.00 DOI 10.1593/tlo.07106",

year = "2008",

month = jan,

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doi = "10.1593/tlo.07106",

language = "English",

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journal = "Translational Oncology",

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T1 - Radiotherapy combined with gemcitabine and oxaliplatin in pancreatic cancer cells

AU - Morgan, Meredith A.

AU - Meirovitz, Amichay

AU - Davis, Mary A.

AU - Kollar, Laura E.

AU - Hassan, Maria C.

AU - Lawrence, Theodore S.

N1 - Funding Information: Address all correspondence to: Meredith A. Morgan, PhD, Department of Radiation Oncology, University of Michigan Medical Center, 1331 East Ann Street, Room 3111 East Ann Building, Ann Arbor, MI 48109-5582, USA. E-mail: [email protected] 1This work was supported by grant no. CA78554 and by the University of Michigan Cancer Center support grant no. 5 P30 CA46592. 2These authors contributed equally to this work. Received 10 July 2007; Revised 1 October 2007; Accepted 5 October 2007 Copyright © 2008 Neoplasia Press, Inc. Open access under CC BY-NC-ND license. 1522-8002/08/$25.00 DOI 10.1593/tlo.07106

PY - 2008/1/1

Y1 - 2008/1/1

N2 - 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.

AB - 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.

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DO - 10.1593/tlo.07106

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JO - Translational Oncology

JF - Translational Oncology

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Radiotherapy combined with gemcitabine and oxaliplatin in pancreatic cancer cells

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