title: The effect of paclitaxel and nab-paclitaxel in combination with anti-angiogenic therapy in breast cancer cell lines.
abstract: 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.
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy, federica_tonissi@yahoo.com.
authors.forename: Federica
authors.initials: F
authors.lastname: Tonissi
authors.forename: Laura
authors.initials: L
authors.lastname: Lattanzio
authors.forename: Marco C
authors.initials: MC
authors.lastname: Merlano
authors.forename: Lucia
authors.initials: L
authors.lastname: Infante
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lo Nigro
authors.forename: Ornella
authors.initials: O
authors.lastname: Garrone
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000068258:Bevacizumab / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015676:Osteonectin / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D015676:Osteonectin; D011960:Receptors, Estrogen; C577241:SPARC protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D017239:Paclitaxel