2015 Volume 6 Issue 2 Pages 263-272
Calcitonin gene-related peptide (CGRP) is widely distributed in the central and peripheral nervous systems and regulates physiological functions. Several neuropeptides are involved in the development and progression of hepatocellular carcinoma (HCC), although the role of CGRP in HCC pathogenesis is unclear. This study attempted to clarify the effects of CGRP on tumor progression in HCC cells. CGRP and its receptors, calcitonin receptor-like receptor and receptor activity-modifying protein-1, were expressed in HCC tissues and HCC cell lines. When Huh7 cells were cultured with CGRP 10−10 and 10−9 M for 24 h, cell proliferation was significantly inhibited. In addition, the total and phosphorylated protein levels of Ras and mitogen-activated protein kinase (MAPK) family proteins, MAP kinase (MEK) 1/2 and extracellular signal-regulated kinase (ERK) 1/2, were also inhibited by CGRP 10−10M incubation. CGRP significantly increased the protein levels of cAMP response element binding protein (CREB) and its phosphorylated form in the nuclei of Huh 7 cells. Furthermore, pretreatment of CGRP receptor antagonist CGRP8–37 abolished the increases in CREB and pCREB protein levels in the nuclei of Huh7 cells. In addition, pretreatment of CGRP8–37 and cAMP inhibitor Rp-cAMP tended to reverse the ERK inhibition in Huh 7 cells cultured with CGRP. These results suggest that CGRP inhibits HCC cell proliferation via CREB activation and Ras/MEK/ERK pathway. CGRP may play an important role in the amelioration of cancer progression.
