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 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 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

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.

In: Anticancer Research, Vol. 19, No. 6 B, 11.1999, p. 5423-5428.

Research output: Contribution to journalArticle

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