Abstract

Abstract Background: Triple-negative breast cancer(TNBC) take up 15% of invasive breast cancer. TNBC has no effective molecular targets & unfavourable prognosis. We investigated the effects of NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, a combine with or not an angiogenesis inhibitor Endostatin in the orthotopic TNBC model & explored its anti-tumor & anti-angiogenesis mechanisms. Material & Methods: Assess sensitivity of the cells to the drug by MTT assays.Orthotopic xenografts were performed for tumor growth and survival studies. Additionally, Immunohistochemistry for VEGF and MVD(CD34) was performed using the EnVision/HRP technique,Serum VEGF was detected by ELISA method. Results: BEZ235 effectively inhibited cell proliferation in vitro & provided additive effects when combine with Endostatin.Treatment with BEZ235 & Endostatin resulted in inhibition of tumor growth & prolongation of survival time of tumor-bearing mice in vivo.Immunohistochemical analysis revealed that intratumoral proliferation & angiogenesis was significantly suppressed. Furthermore, Changing of the number of Serum VEGF support the finding of angiogenesis inhibition too. Conclusion: Our findings suggest that BEZ235 exerts antitumor effects against TNBC & enhances effects of Endostatin through inhibition of cell proliferation & tumor angiogenesis. This approach may represent a promising combination targeted therapy for TNBC treatment. Note: This abstract was not presented at the meeting. Citation Format: Xiaoshan Wang, Xiao Zhang, Fanghua Li. The combination of NVP-BEZ235 & endostatin exerts synergistic anticancer activity against triple-negative breast cancer in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3908.

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