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The effect of paclitaxel and nab-paclitaxel in combination with anti-angiogenic therapy in breast cancer cell lines

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Summary

Taxanes represent a treatment of choice for metastatic breast cancer. Their combination with bevacizumab improved response rate and progression-free survival. We studied in vitro the effect on cell survival of the combination of either paclitaxel or nab-paclitaxel with bevacizumab and we investigated the biological factors involved in the response to treatments. We used two breast cancer cell lines, MCF7 (ER+/HER2-) and MDA-MB-231 (ER-/HER2-), co-cultured with or without HUVEC cells. We analysed cell survival by MTT test, VEGF secretion by ELISA and VEGFR, SPARC, MDR1 expression by western blot. Doses of both taxanes causing a 50 % growth inhibition were higher in MCF7 than MDA-MB-231, suggesting that taxanes are more effective in ER- cell lines. When both cell lines were grown as single culture, the combination bevacizumab+paclitaxel showed a similar anti-proliferative effect compared to paclitaxel alone. The association bevacizumab+nab-paclitaxel was more effective than nab-paclitaxel alone. An increased anti-proliferative effect of bevacizumab+paclitaxel was observed when MDA-MB-231 cells were cultured with HUVEC. We detected an induction of VEGF secretion when MDA-MB-231 cells were treated with either taxanes. Paclitaxel caused a reduction of VEGF in MCF7. SPARC resulted up-regulated in both cell lines treated with bevacizumab+nab-paclitaxel. Nab-paclitaxel seems to play an important role in inhibiting tumor proliferation through albumin-SPARC bound in association with bevacizumab compared to taxanes alone in both breast cancer cells. The addition of bevacizumab to paclitaxel increased its activity only in ER- cells. This difference might be due to their ER status.

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Acknowledgments

We thank O. Barbieri (IRCCS Ospedale S. Martino, Genoa, Italy) for helpful discussion of scientific data and D. Preston for his kindly revision of English.

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The authors declare that they have no conflict of interest

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This article does not contain any studies with human participants or animals performed by any of the authors

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    Authors and Affiliations

    1. Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy

      Federica Tonissi, Laura Lattanzio & Cristiana Lo Nigro

    2. Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy

      Marco C. Merlano & Ornella Garrone

    3. Pharmacy, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy

      Lucia Infante

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    1. Federica Tonissi
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    2. Laura Lattanzio
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    Correspondence to Cristiana Lo Nigro.

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    Federica Tonissi and Laura Lattanzio contributed equally to this work.

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    Tonissi, F., Lattanzio, L., Merlano, M.C. et al. The effect of paclitaxel and nab-paclitaxel in combination with anti-angiogenic therapy in breast cancer cell lines. Invest New Drugs 33, 801–809 (2015). https://doi.org/10.1007/s10637-015-0249-z

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    • DOI: https://doi.org/10.1007/s10637-015-0249-z

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