1596P - Paclitaxel/nab-paclitaxel in combination with anti-angiogenic therapy: An in vitro study

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Basic Science
Presenter Cristiana Lo Nigro
Citation Annals of Oncology (2014) 25 (suppl_4): iv546-iv563. 10.1093/annonc/mdu358
Authors C. Lo Nigro, O. Garrone, F. Tonissi, L. Lattanzio, A. Ghiglia, D. Vivenza, M. Monteverde, M.C. Merlano
  • Oncology, S. Croce General Hospital, 1200 - Cuneo/IT

Abstract

Aim

Taxanes are the treatment of choice of metastatic breast cancer and their combination with the anti-angiogenic drug bevacizumab improved response rate (RR) and progression-free survival (PFS). In this contest, we decided to study in vitro the effect on cell survival of the combination of paclitaxel/nab-paclitaxel with bevacizumab and related biological factors, including SPARC (vehicle protein involved in nab-paclitaxel uptake) VEGF/R at basal level and after treatments.

Methods

We used 2 different breast cancer cell lines, MCF7 (ER+/HER2-) and MM231 (ER-/HER2-) together with HUVEC endothelial cells (Human Umbilical Vein Endothelial Cell), seeded in transwell plates. We analysed cell survival by MTT test, VEGF secretion by ELISA assay and proteins expression by western blot (VEGFR, SPARC).

Results

Seeding MCF7 with HUVEC, only the combination bevacizumab+nab-paclitaxel showed a higher effect than nab-paclitaxel alone (p<0.01), while the same effect of paclitaxel was obtained when given either alone or in combination with bevacizumab. In MM231 seeded with HUVEC both the combinations showed a significant reduction of survival compared to the two taxanes alone (p<0.05). We also detected an induction of VEGF secretion when MM231 were treated with nab-paclitaxel or paclitaxel (respectively p<0.001 and p<0.01); this effect was not seen in MCF7. Analysis on MCF7 by western blot showed an induction of SPARC protein expression only when cells were treated with both combinations (p<0.05). In MM231 the upregolation of SPARC protein expression was seen only when cells were treated with bevacizumab+nab-paclitaxel (p<0.05).

Conclusions

Our results confirmed that nab-paclitaxel could play an important role in inhibiting tumour proliferation through albumin-SPARC bound when administered with bevacizumab compared to the taxane alone. Moreover in ER+ cells bevacizumab+nab-paclitaxel demonstrated a higher effect than bevacizumab+paclitaxel in respect to the corresponding taxanes alone. All together these results suggested that further clinical trials could be proposed to deeply investigate the combination of nab-paclitaxel and anti-angiogenic therapy in a specific group of ER+ breast cancer patients

Disclosure

All authors have declared no conflicts of interest.