Jiguang Ma
First Affiliated Hospital of Xi’an Jiaotong University, China
Title: Sonic hedgehog signaling pathway promotes pancreatic cancer pain via nerve growth factor
Biography
Biography: Jiguang Ma
Abstract
Many pancreatic cancer (PC) patients suffer from abdominal pain and back pain. However, the cause of pain associated with PC is largely unclear. In this study, we tested the potential influence of the sonic hedgehog (sHH) signaling pathway on PC pain. Substance P (SP) and calcitonin gene-related peptide (CGRP) expression was measured in cultured PC cells and dorsal root ganglions (DRGs) by real-time PCR, western blotting analysis and ELISA. Small interfering RNA transfection and plasmid constructs were used to regulate the expression of sHH in the AsPc-1 and Panc-1 cell lines. Pain-related behavior was observed in an orthotopic tumor model in nude mice. In this study, the results showed that sHH increased the expression of SP and CGRP in DRGs in a concentration and time-dependent manner. Additionally, sHH secretion from PC cells could activate sHH signaling pathway and in turn, increase the expression of nerve growth factor (NGF), P75 and TrkA in DRGs. Furthermore, sHH signaling pathway and NGF/NGF receptor contributed to pain factors and pain behavior. Our results demonstrate that PC pain originates from sHH signaling pathway, and NGF mediates the pain mechanism via regulating SP and CGRP.