Effect of propranolol on the expression of growth factors and apoptotic factors related to infantile hemangiomas

Objective　To investigate the effects of propranolol on the expression of growth factors and apoptotic factors related to infantile hemangiomas, and explore the underlying mechanisms for treatment of hemangiomas by propranolol. Methods　Oral propranolol was administered to 39 patients ≤3 months with hemangiomas during the proliferative phase, and they were in accordance with the inclusion criteria of the treatment. Patients who had contraindications to treatment were excluded, and informed consent from their family members was obtained. Biopsy of the lesion under local anesthesia was done before medication. The oral dose of propranolol was 1mg/kg per 12 hours. After 8 weeks of treatment, the hemangioma was resected. The specimens taken before and after treatment were scrutinized for changes in tissue structure and cell form after HE staining. The expressions of the proteins ADRB1, ADRB2, ERK, Akt, NF-κB, VEGFA, Cyclin D1, Cyclin E1, Ki-67, Bax, Bcl-2, caspase-8, Fas, FasL, caspase-9, and caspase-3 in the focal tissue were determined with immunohistochemistry and real-time fluorescence quantitative RT-PCR. At the same time, the microvessel density (MVD) value, Ki-67 index and apoptosis index before and after treatment were also determined and compared using CD34, Ki-67 and TUNEL staining technique, respectively. Meanwhile, the mRNA expressions of these factors were assessed with quantitative real-time RT-PCR. Results　After 8 weeks of treatment, all the protein content and mRNA expressions of ADRB1, ADRB2, ERK, Akt, NF-κB, VEGFA, Cyclin D1, Cyclin E1, Ki-67, Bcl-2, and MVD value and Ki-67 index were decreased significantly (P<0.01), while the protein and mRNA expressions of Bax, caspase-3, caspase-9, and apoptosis index were increased significantly (P<0.01). However, there was no obvious change in the expressions of Fas, FasL and caspase-8 after treatment. Conclusion　Propranolol can inhibit proliferation and promot intrinsic apoptotic pathway of hemangioma through regulating the MAPKs and PI3K-Akt pathways, but it shows no influence on the extrinsic apoptotic pathway. DOI: 10.11855/j.issn.0577-7402.2015.02.07