Supplementary Figures 1-6 from Rac1/Pak1/p38/MMP-2 Axis Regulates Angiogenesis in Ovarian Cancer

Gonzalez-Villasana, Vianey; Fuentes-Mattei, Enrique; Ivan, Cristina; Dalton, Heather J.; Rodriguez-Aguayo, Cristian; Fernandez-de Thomas, Ricardo J.; Aslan, Burcu; del C. Monroig, Paloma; Velazquez-Torres, Guermarie; Previs, Rebecca A.; Pradeep, Sunila; Kahraman, Nermin; Wang, Huamin; Kanlikilicer, Pinar; Ozpolat, Bulent; Calin, George; Sood, Anil K.; Lopez-Berestein, Gabriel

doi:10.1158/1078-0432.22459323.v1

- No file added yet -

Supplementary Figures 1-6 from Rac1/Pak1/p38/MMP-2 Axis Regulates Angiogenesis in Ovarian Cancer

journal contribution

posted on 2023-03-31, 18:49 authored by Vianey Gonzalez-Villasana, Enrique Fuentes-Mattei, Cristina Ivan, Heather J. Dalton, Cristian Rodriguez-Aguayo, Ricardo J. Fernandez-de Thomas, Burcu Aslan, Paloma del C. Monroig, Guermarie Velazquez-Torres, Rebecca A. Previs, Sunila Pradeep, Nermin Kahraman, Huamin Wang, Pinar Kanlikilicer, Bulent Ozpolat, George Calin, Anil K. Sood, Gabriel Lopez-Berestein

Supplementary Figures 1-6. Supplementary Figure S1: In vivo and in vitro effects of ZA on apoptosis. Supplementary Figure S2: Nab-paclitaxel inhibits tube formation.Supplementary Figure S3: RPPA analysis in HeyA8 MDR treated with ZA. Supplementary Figure S4: Functional changes induced by ZA in HeyA8 MDR. Supplementary Figure S5: ZA decreases angiogenic factors. Supplementary Figure S6: ZA inhibits cell invasion

History

ARTICLE ABSTRACT

Purpose: Zoledronic acid is being increasingly recognized for its antitumor properties, but the underlying functions are not well understood. In this study, we hypothesized that zoledronic acid inhibits ovarian cancer angiogenesis preventing Rac1 activation.Experimental Design: The biologic effects of zoledronic acid were examined using a series of in vitro [cell invasion, cytokine production, Rac1 activation, reverse-phase protein array, and in vivo (orthotopic mouse models)] experiments.Results: There was significant inhibition of ovarian cancer (HeyA8-MDR and OVCAR-5) cell invasion as well as reduced production of proangiogenic cytokines in response to zoledronic acid treatment. Furthermore, zoledronic acid inactivated Rac1 and decreased the levels of Pak1/p38/matrix metalloproteinase-2 in ovarian cancer cells. In vivo, zoledronic acid reduced tumor growth, angiogenesis, and cell proliferation and inactivated Rac1 in both HeyA8-MDR and OVCAR-5 models. These in vivo antitumor effects were enhanced in both models when zoledronic acid was combined with nab-paclitaxel.Conclusions: Zoledronic acid has robust antitumor and antiangiogenic activity and merits further clinical development as ovarian cancer treatment. Clin Cancer Res; 21(9); 2127–37. ©2015 AACR.