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

• Published in: Investigational new drugs Vol. 33; no. 4; pp. 801 - 809
• Main Authors: Tonissi, Federica, Lattanzio, Laura, Merlano, Marco C., Infante, Lucia, Lo Nigro, Cristiana, Garrone, Ornella
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2015; Springer Nature B.V
• Subjects: Albumins - pharmacology; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Antineoplastic Agents, Phytogenic - pharmacology; Bevacizumab - pharmacology; Breast cancer; Breast Neoplasms - metabolism; Cancer therapies; Cell Line, Tumor; Cell Proliferation - drug effects; Cells; Cells, Cultured; Chemotherapy; Clinical trials; Coculture Techniques; Drug dosages; Drugs; Female; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Medicine; Medicine & Public Health; Metastasis; Mutation; Oncology; Osteonectin - metabolism; Paclitaxel - pharmacology; Pharmacology/Toxicology; Pharmacy; Preclinical Studies; Receptors, Estrogen - metabolism; Receptors, Vascular Endothelial Growth Factor - metabolism; Response rates; Solvents; Studies; Teaching hospitals; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Italy; Metastatic breast cancer; SPARC; VEGF; Nab-paclitaxel; Paclitaxel; Bevacizumab
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-015-0249-z

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.