Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines

Hamid R. Bahadori, Caio Max S Rocha Lima, Mark R. Green, Ahmad R. Safa

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Gemcitabine (2',2'-difluorodeoxycytidine, dFdC), an analog of deoxycytidine, is an antineoplastic agent with clinical activity against several types of cancer. Irinotecan (CPT-11), a topoisomerase I inhibitor, is a drug with a broad spectrum of anticancer activity. Since these drugs have different mechanisms of cytotoxicity and dose-limiting toxicity profiles, preclinical combination studies were performed on the MCF-7 breast cancer and the SCOG small cell lung cancer (SCLC) cell lines. Both gemcitabine and CPT-11 as single agents were effective growth inhibitors in these cell lines. Isobologram analysis revealed for the first time that the combination of these drugs exerted synergy over a wide range of concentrations in MCF-7 and SCOG cells. Moreover, combination index (CI) analysis revealed that at low concentrations, combinations of gemcitabine and CPT-11 show a synergistic growth inhibitory effect on MCF-7 cells. However, in SCOG cells CI analysis showed synergy at concentrations of gemcitabine and CPT-11 greater than 1 μM but antagonism at combination concentrations less than 1 μM. These preclinical cytotoxicity data provide an experimental basis for conducting clinical trials using combinations of gemcitabine and CPT-11, especially in patients with breast and lung cancers.

Original languageEnglish
Pages (from-to)5423-5428
Number of pages6
JournalAnticancer Research
Volume19
Issue number6 B
StatePublished - Nov 1 1999

Fingerprint

irinotecan
gemcitabine
Small Cell Lung Carcinoma
Breast
Cell Line
MCF-7 Cells
Topoisomerase I Inhibitors
Breast Neoplasms
Growth Inhibitors
Deoxycytidine
Drug Combinations
Pharmaceutical Preparations
Antineoplastic Agents
Lung Neoplasms

Keywords

  • Breast cancer
  • CPT-11
  • Gemcitabine
  • Irinotecan
  • Small cell lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bahadori, H. R., Rocha Lima, C. M. S., Green, M. R., & Safa, A. R. (1999). Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines. Anticancer Research, 19(6 B), 5423-5428.

Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines. / Bahadori, Hamid R.; Rocha Lima, Caio Max S; Green, Mark R.; Safa, Ahmad R.

In: Anticancer Research, Vol. 19, No. 6 B, 01.11.1999, p. 5423-5428.

Research output: Contribution to journalArticle

Bahadori, HR, Rocha Lima, CMS, Green, MR & Safa, AR 1999, 'Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines', Anticancer Research, vol. 19, no. 6 B, pp. 5423-5428.
Bahadori, Hamid R. ; Rocha Lima, Caio Max S ; Green, Mark R. ; Safa, Ahmad R. / Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines. In: Anticancer Research. 1999 ; Vol. 19, No. 6 B. pp. 5423-5428.
@article{a4dece0074fc49cdb0f8c74c5e4a65e0,
title = "Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines",
abstract = "Gemcitabine (2',2'-difluorodeoxycytidine, dFdC), an analog of deoxycytidine, is an antineoplastic agent with clinical activity against several types of cancer. Irinotecan (CPT-11), a topoisomerase I inhibitor, is a drug with a broad spectrum of anticancer activity. Since these drugs have different mechanisms of cytotoxicity and dose-limiting toxicity profiles, preclinical combination studies were performed on the MCF-7 breast cancer and the SCOG small cell lung cancer (SCLC) cell lines. Both gemcitabine and CPT-11 as single agents were effective growth inhibitors in these cell lines. Isobologram analysis revealed for the first time that the combination of these drugs exerted synergy over a wide range of concentrations in MCF-7 and SCOG cells. Moreover, combination index (CI) analysis revealed that at low concentrations, combinations of gemcitabine and CPT-11 show a synergistic growth inhibitory effect on MCF-7 cells. However, in SCOG cells CI analysis showed synergy at concentrations of gemcitabine and CPT-11 greater than 1 μM but antagonism at combination concentrations less than 1 μM. These preclinical cytotoxicity data provide an experimental basis for conducting clinical trials using combinations of gemcitabine and CPT-11, especially in patients with breast and lung cancers.",
keywords = "Breast cancer, CPT-11, Gemcitabine, Irinotecan, Small cell lung cancer",
author = "Bahadori, {Hamid R.} and {Rocha Lima}, {Caio Max S} and Green, {Mark R.} and Safa, {Ahmad R.}",
year = "1999",
month = "11",
day = "1",
language = "English",
volume = "19",
pages = "5423--5428",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "6 B",

}

TY - JOUR

T1 - Synergistic effect of gemcitabine and irinotecan (CPT-11) on breast and small cell lung cancer cell lines

AU - Bahadori, Hamid R.

AU - Rocha Lima, Caio Max S

AU - Green, Mark R.

AU - Safa, Ahmad R.

PY - 1999/11/1

Y1 - 1999/11/1

N2 - Gemcitabine (2',2'-difluorodeoxycytidine, dFdC), an analog of deoxycytidine, is an antineoplastic agent with clinical activity against several types of cancer. Irinotecan (CPT-11), a topoisomerase I inhibitor, is a drug with a broad spectrum of anticancer activity. Since these drugs have different mechanisms of cytotoxicity and dose-limiting toxicity profiles, preclinical combination studies were performed on the MCF-7 breast cancer and the SCOG small cell lung cancer (SCLC) cell lines. Both gemcitabine and CPT-11 as single agents were effective growth inhibitors in these cell lines. Isobologram analysis revealed for the first time that the combination of these drugs exerted synergy over a wide range of concentrations in MCF-7 and SCOG cells. Moreover, combination index (CI) analysis revealed that at low concentrations, combinations of gemcitabine and CPT-11 show a synergistic growth inhibitory effect on MCF-7 cells. However, in SCOG cells CI analysis showed synergy at concentrations of gemcitabine and CPT-11 greater than 1 μM but antagonism at combination concentrations less than 1 μM. These preclinical cytotoxicity data provide an experimental basis for conducting clinical trials using combinations of gemcitabine and CPT-11, especially in patients with breast and lung cancers.

AB - Gemcitabine (2',2'-difluorodeoxycytidine, dFdC), an analog of deoxycytidine, is an antineoplastic agent with clinical activity against several types of cancer. Irinotecan (CPT-11), a topoisomerase I inhibitor, is a drug with a broad spectrum of anticancer activity. Since these drugs have different mechanisms of cytotoxicity and dose-limiting toxicity profiles, preclinical combination studies were performed on the MCF-7 breast cancer and the SCOG small cell lung cancer (SCLC) cell lines. Both gemcitabine and CPT-11 as single agents were effective growth inhibitors in these cell lines. Isobologram analysis revealed for the first time that the combination of these drugs exerted synergy over a wide range of concentrations in MCF-7 and SCOG cells. Moreover, combination index (CI) analysis revealed that at low concentrations, combinations of gemcitabine and CPT-11 show a synergistic growth inhibitory effect on MCF-7 cells. However, in SCOG cells CI analysis showed synergy at concentrations of gemcitabine and CPT-11 greater than 1 μM but antagonism at combination concentrations less than 1 μM. These preclinical cytotoxicity data provide an experimental basis for conducting clinical trials using combinations of gemcitabine and CPT-11, especially in patients with breast and lung cancers.

KW - Breast cancer

KW - CPT-11

KW - Gemcitabine

KW - Irinotecan

KW - Small cell lung cancer

UR - http://www.scopus.com/inward/record.url?scp=0033368083&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033368083&partnerID=8YFLogxK

M3 - Article

VL - 19

SP - 5423

EP - 5428

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 6 B

ER -