Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

Int J Oncol. 2019 Dec;55(6):1296-1312. doi: 10.3892/ijo.2019.4887. Epub 2019 Sep 30.


Angiogenesis has an important role in tumour cell growth and metastasis. Anisomycin has been shown to inhibit tumour cell growth. However, whether anisomycin can inhibit angiogenesis of tumours has not been reported. The present study demonstrated that there was a positive correlation between tumour angiogenesis and the number of CD44+/CD133+ serous human ovarian cancer stem cells (HuOCSCs). Subsequently, it was confirmed that anisomycin significantly inhibited the proliferation, invasion, tumorigenic ability and tumour angiogenesis of HuOCSCs. Gene expression profiling by cDNA microarrays revealed that the expression levels of vascular endothelial cell markers, platelet‑derived growth factors, Notch pathway components and 27 tumour angiogenesis‑related genes were significantly decreased in the anisomycin‑treated group compared with the control group. Further experiments demonstrated that the expression levels of endogenous long non‑coding RNA (lncRNA) maternally expressed 3 (Meg3) were significantly decreased in anisomycin‑treated HuOCSCs, whereas the expression levels of microRNA (miR)‑421 were significantly increased. The results of luciferase reporter assays indicated that, when miR‑421 was overexpressed in cells, the luciferase activities of wild‑type platelet derived growth factor receptor α (PDGFRA) 3' untranslated region and Meg3 reporter plasmids were significantly decreased. Overexpression of miR‑421 in HuOCSCs significantly enhanced the anisomycin‑mediated inhibition of HuOCSC proliferation. Taken together, the present results demonstrated that anisomycin inhibited the activation downstream of the Notch1 pathway by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis, ultimately inhibiting angiogenesis, proliferation and invasion in ovarian cancer cells.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Anisomycin / pharmacology*
  • Anisomycin / therapeutic use
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics
  • Carcinoma, Ovarian Epithelial / blood supply
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Drug Screening Assays, Antitumor
  • Embryo, Nonmammalian
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Mice
  • MicroRNAs / agonists
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • Neoplastic Stem Cells
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Physiologic / drug effects
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Ovary / pathology
  • Primary Cell Culture
  • RNA, Long Noncoding / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • Zebrafish


  • 3' Untranslated Regions
  • MEG3 non-coding RNA, human
  • MIRN421 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Anisomycin
  • Receptor, Platelet-Derived Growth Factor alpha