Abstract A56: Metformin targets Rho GTPases to inhibit neuroblastoma cell growth; implications in the treatment of neuroblastoma

In recent years, oncologists are paying considerable attention to metformin (N', N'-dimethylbiguanide) in the treatment of various types of cancers, as some population-based studies have shown low cancer incidences and mortalities among diabetic-patients treated with metformin. In the present study, using neuroblastoma cells, we explored the anti-tumor activity and the underlying mechanisms of metformin. Neuroblastoma is a malignant cancer of the postganglionic sympathetic nervous system; it develops in the adrenal gland and metastasizes to liver, bone, bone marrow, lymph nodes, neck and chest. It is the most common cancer in infants younger than one and second most common tumors in children. In the United States of America, it accounts for 7% of all childhood cancers, and is responsible for 15% of all cancer deaths in children younger than 15 years. Various genetic and cytological alterations allow cells to develop drug resistance and help neuroblastoma tumors to escape most available therapies.Using human neuroblastoma cells of different genotypes (SH-SY5Y, MYCN-nonamplified; and SK-N-BE(2), MYCN-amplified cells), we generated subcutaneous xenograft mice models, and metformin (50, 100 and 250 mg/kg body weight per mice) was given daily by oral gavage to tumor-bearing mice. Our in vivo results demonstrated that metformin (100 and 250 mg/kg body weight) significantly inhibited the growth of tumors in both mice models. Immunofluorescence and Western blot results indicated redu...
Source: Cancer Prevention Research - Category: Cancer & Oncology Authors: Tags: Pediatric Malignancies: Poster Presentations - Proffered Abstracts Source Type: research