Propranolol inhibits the activity of PI3K, AKT, and HIF-1α in infantile hemangiomas

Pediatr Surg Int. 2018 Nov;34(11):1233-1238. doi: 10.1007/s00383-018-4347-9. Epub 2018 Sep 19.

Abstract

Purpose: We sought to evaluate effect of propranolol in the treatment of infantile hemangiomas by quantifying the amount of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and hypoxia-inducible factor-1α (HIF-1α).

Methods: Hemangioma tissue was isolated from an infant patient and implanted into nude mice to establish a hemangioma model. Twenty-four hemangioma-model nude mice were divided into two groups including a control group (saline, by gastrogavage) and an experimental group (propranolol, by gastrogavage). The hemangioma-model nude mice were euthanized and tumors were removed at 30 and 50 days (before and after treatment). HE staining was used to observe the histopathological changes, and western blot and quantitative real-time PCR were used to describe levels of protein and mRNA expression of PI3K, AKT, and HIF-1α.

Results: Propranolol treatment decreased tumor size as compared to the control group. Protein and mRNA expression levels of PI3K, AKT, and HIF-1α were lower in the experimental group at day 50 compared to the control group at day 50 and the experimental group at day 30 (p < 0.05).

Conclusion: Propranolol can promote regression of infantile hemangiomas, which may be related to the inhibition of PI3K, AKT, and HIF-1α activity.

Keywords: AKT; HIF-1α; Hemangioma; PI3K; Propranolol.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Hemangioma / drug therapy*
  • Hemangioma / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / drug effects*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mice, Nude
  • Phosphatidylinositol 3-Kinase / drug effects*
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism
  • Propranolol / pharmacology*
  • Proto-Oncogene Proteins c-akt / drug effects*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / metabolism
  • Vasodilator Agents / pharmacology*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Vasodilator Agents
  • Propranolol
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt