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Combination analyses of anti-cancer drugs on human neuroendocrine tumor cell lines

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Abstract

Purpose

There is a large need for better pharmacological treatment of neuroendocrine tumors. The aim of this study was to investigate and quantify the cytotoxic potentiating effects resulting from a combination of five substances, NSC 95397, emetine, CGP-74514A hydrochloride, Brefeldin A and sanguinarine chloride, chosen from a previous screening of 1,280 pharmacologically active agents on neuroendocrine tumor cells, with standard cytotoxic agents currently used in the treatment of neuroendocrine tumors.

Method

The human pancreatic carcinoid cell line BON-1, human typical bronchial carcinoid cell line NCI-H727 and the human atypical bronchial carcinoid cell line NCI-H720 were used. Combinations between doxorubicin, etoposide, oxaliplatin, docetaxel, and each one of the five agents were studied and simultaneous exposures were explored using the median-effect method.

Results

Most of the combinations of NSC-95397 and emetine with doxorubicin, etoposide, docetaxel, and oxaliplatin showed synergism, and their remaining combinations were additive. Almost all of the CGP-74514A hydrochloride interactions were additive, while brefeldin A and sanguinarine displayed less synergy but more additive and antagonistic interactions in combination with the standard drugs.

Conclusion

The synergistic and additive interactions make NSC-95397, emetine, and CGP-74514A hydrochloride potential candidates for incorporation into combination chemotherapy regimens and these drugs might be the suitable candidates for further clinical studies in patients with bronchial carcinoids and pancreatic endocrine tumors.

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Acknowledgments

The authors thank Linda Rickardson, Malin Wickström, and Lena Lenhammar for valuable technical assistance. This study was financially supported by grants from Lions Cancer Research Fund at Uppsala University Hospital.

Conflict of interest statement

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Endocrine Oncology, Faculty of Medicine, University of Uppsala, University Hospital, 751 85, Uppsala, Sweden

    Dhana E. Larsson, Kjell Öberg & Dan Granberg

  2. Department of Medical Sciences, Division of Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden

    Sadia Hassan & Rolf Larsson

Authors
  1. Dhana E. Larsson
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  2. Sadia Hassan
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  3. Rolf Larsson
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  4. Kjell Öberg
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  5. Dan Granberg
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Correspondence to Dhana E. Larsson.

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Larsson, D.E., Hassan, S., Larsson, R. et al. Combination analyses of anti-cancer drugs on human neuroendocrine tumor cell lines. Cancer Chemother Pharmacol 65, 5–12 (2009). https://doi.org/10.1007/s00280-009-0997-6

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  • DOI: https://doi.org/10.1007/s00280-009-0997-6

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