Issue (if applicable)
In the 25 years since temozolomide entered phase I clinical trials, few new primary or adjuvant therapies have been developed for the treatment of glioblastoma multiforme (GBM) tumors. Our laboratory has been exploring novel methods for the treatment of GBMs. Recent studies indicate that the expression of the hormone leptin and its receptor (OBR) increases in gliomas and positively correlates with the malignancy of the tumor. Interestingly, ß3-adrenergic receptor agonists are known to decrease leptin expression in adipocytes but have not been examined in GBM cells. We hypothesized that b3-adrenergic agonists downregulate the expression of leptin and its receptor. In our studies, the relative expression of leptin, OBR, and ß3 adrenergic receptor were measured in the GBM cell lines T98G and LN229 using quantitative real-time PCR. Gene expression levels in untreated cells were compared with those of cells treated with 400 ng/mL of a selective ß3 agonist (BRL 37344). The results indicate that the relative expression of leptin in the ß3 agonist-treated cells was reduced 27-43%when compared with controls (T98: 0.73, [0.59-0.89]; LN229: 0.57 [0.55-0.59]). Similarly, expression of the leptin receptor was reduced 31-39% when compared with controls (T98: 0.69 [0.63-0.75]; LN229: 0.63 [0.56-0.71]). These results suggest that the use of ß3-adrenergic agonists may be beneficial for patients with GBM tumors by downregulating tumor-derived leptin and leptin signaling through the leptin receptor.
Johnathan E. Lawrence, Nicholas J. Cook, Richard A. Rovin, Robert J. Belton, and Robert J. Winn. "Effects of ß3-adrenergic receptor agonist on gene expression of leptin in glioblastoma" Neuro-Oncology 14.suppl 6 (2012): vi7-vi20. Available at: http://works.bepress.com/johnathan_lawrence/3