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 journalArticlepeer-review

43 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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