Phosphoinositide 3-kinase/Akt pathway is involved in pingyangmycin-induced growth inhibition, apoptosis and reduction of invasive potential in EOMA mouse hemangioendothelioma cells

Abstract

Pingyangmycin (PYM), a glycopeptide antibiotic, has been recommended as a stand treatment for hemangioma. However, the underlying mechanisms of its anti‑tumor effects have remained elusive. The purpose of the present study was to explore the effects of PYM on the biological behavior of the EOMA mouse hemangioendothelioma cell line and investigate the possible mechanisms. The effects of PYM on EOMA cell viability were determined by an MTT assay, apoptosis was evaluated by Annexin V/propidium iodide staining and flow cytometric analysis, and cell invasion ability was determined using a Transwell invasion assay. In order to investigate the underlying mechanism of action of PYM, the expression of angiogenic signaling proteins was determined by western blot analysis. PYM treatment (0.5‑500 µg/ml) inhibited cell growth in a time- and dose‑dependent manner. PYM at 100 µg/ml significantly induced apoptosis and reduced the invasive ability of EOMA cells. Effects of PYM on cell viability, apoptosis and invasion ability were completely blocked by co‑treatment with phosphoinositide 3‑kinase (PI3K) activator insulin‑like growth factor‑1 (IGF‑1). Furthermore, treatment with PYM reduced the expression of PI3K and phosphorylated Akt. In conclusion, the present study indicated that the PI3K/Akt pathway is likely to be involved in the anti-cancer effects of PYM on EOMA cells.

Integrin β3/Akt signaling contributes to platelet-induced hemangioendothelioma growth

“…The EOMA cell line closely mimics the HE condition, responding to angiogenic regulators 5, 6 , inducing vessel formation, and promoting development of KMS in mice 7 . Therefore, a number of studies have utilized this cell line in order to examine the therapeutic potential of a variety of factors 8–11 . Moreover, examination of endogenous factors expressed by EOMA cells that increase angiogenesis such as insulin-like growth factor 2, 3-phosphoinositide-dependent kinase 1, transcription factor Prox1, and monocyte chemoattractant protein-1, has also provided important clues to HE progression 12–16 .…”

Troponin-I localizes selected apico-basal cell polarity signals

“…Searching for additional mechanisms involved in the localization of polarity factors, we noticed that mammalian PI3K mediates AB polarity in epithelial cells and contributes to basal membrane formation (Peng et al, 2015). Thus, we analyzed the potential effects of PI3K depletion in wing disc cells and found no alterations in the apical localization of TnI, Par3, or in the basal localization of Dlg ( Suppl.…”

Pingyangmycin Pretreatment Influences the Biological Behavior of Ocular Venous Malformation and Relates with Galectin-3 Expression

“…Moreover, pingyangmycin shows less toxicity and side effects in the treatment of venous malformation. [910] As a result, it has been used as an effective standard therapy for severe venous malformation which cannot be removed by surgery. [18] Furthermore, pingyangmycin treatment reduced the lesions of ocular venous malformation, accompanied by a decrease in Gal-3 expression.…”

“…[910] In this study, we compared the expression levels of Gal-3 in patients with ocular venous malformation who were given pingyangmycin injection before surgery and those who did not receive pingyangmycin pretreatment. One purpose of this study was to investigate the expression levels of Gal-3 in patients with ocular venous malformation.…”