4.6 Article

Co-targeting triple-negative breast cancer cells and endothelial cells by metronomic chemotherapy inhibits cell regrowth and migration via downregulation of the FAK/VEGFR2/VEGF axis and autophagy/apoptosis activation

期刊

FRONTIERS IN ONCOLOGY
卷 12, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.998274

关键词

metronomic chemotherapy; triple negative breast cancer (TNBC); endothelial cells; angiogenesis; FAK-VEGFR2-VEGF-axis

类别

资金

  1. A&Q- Polo per la Qualificazione del Sistema Agro-Industriale per indagini di laboratorio collegate allo studio pre-clinico in vitro VICTOR-9
  2. Horizon 2020 Instand-NGS4P [874719]
  3. MIUR, PRIN
  4. Italian Ministry of Health Ricerca Corrente-IRCCS MultiMedica
  5. Italian Association for Cancer Research (AIRC-MFAG) [22818]
  6. Cariplo Foundation [2019-1609]

向作者/读者索取更多资源

The study found that metronomic chemotherapy (mCHT) with 5-Fluorouracil plus Vinorelbine (5-FU+VNR) is more effective than standard treatment (STD) in controlling the proliferation, survival, migration, and invasion of endothelial cells (ECs) and triple-negative breast cancer (TNBC) cells. It also has a strong anti-angiogenic effect. The data suggest that the stabilization of tumor growth observed in TNBC patients treated with mCHT is likely due to its direct cytotoxic effects as well as its anti-metastatic and anti-angiogenic effects.
High-dose standard-of-care chemotherapy is the only option for triple-negative breast cancer (TNBC) patients, which eventually die due to metastatic tumors. Recently, metronomic chemotherapy (mCHT) showed advantages in treating TNBCs leading us to investigate the anti-metastatic and anti-angiogenic potential of metronomic 5-Fluorouracil plus Vinorelbine (5-FU+VNR) on endothelial cells (ECs) and TNBCs in comparison to standard treatment (STD). We found that 10-fold lower doses of 5-FU+VNR given mCHT vs. STD inhibits cell proliferation and survival of ECs and TNBC cells. Both schedules strongly affect ECs migration and invasion, but in TNBC cells mCHT is significantly more effective than STD in impairing cell migration and invasion. The two treatments disrupt FAK/VEGFR/VEGF signaling in both ECs and TNBC cells. mCHT, and to a much lesser extent STD treatment, induces apoptosis in ECs, whereas it switches the route of cell death from apoptosis (as induced by STD) to autophagy in TNBC cells. mCHT-treated TNBCs-derived conditioned medium also strongly affects ECs' migration, modulates different angiogenesis-associated proteins, and hampers angiogenesis in matrix sponge in vivo. In conclusion, mCHT administration of 5-FU+VNR is more effective than STD schedule in controlling cell proliferation/survival and migration/invasion of both ECs and TNBC cells and has a strong anti-angiogenic effect. Our data suggest that the stabilization of tumor growth observed in TNBC patients treated with mCHT therapy schedule is likely due not only to direct cytotoxic effects but also to anti-metastatic and anti-angiogenic effects.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据