Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2321
Revised: December 23, 2013
Accepted: January 20, 2014
Published online: March 7, 2014
Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1- and 5-year relative survival rates are 25% and 6%, respectively. Thus, it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients. The peptide substance P (SP) has a widespread distribution throughout the body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates biological functions related to cancer, such as tumor cell proliferation, neoangiogenesis, the migration of tumor cells for invasion, infiltration and metastasis, and it exerts an antiapoptotic effects on tumor cells. It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression: (1) pancreatic cancer cells and samples express NK-1 receptors; (2) the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells; (3) nanomolar concentrations of SP induce pancreatic cancer cell proliferation; (4) NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner, at a certain concentration, these antagonists inhibit 100% of tumor cells; (5) this antitumor action is mediated through the NK-1 receptor, and tumor cells die by apoptosis; and (6) NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts. All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer; that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer, and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.
Core tip: The substance P (SP)/neurokinin-1 (NK-1) receptor system plays an important role in pancreatic cancer progression. Pancreatic cancer cells overexpress NK-1 receptors and SP promotes angiogenesis and the proliferation and the migration of pancreatic tumor cells. By contrast, NK-1 receptor antagonists, in a concentration-dependent manner, inhibit pancreatic cell proliferation (tumor cells die by apoptosis), have antiangiogenic properties in pancreatic cancer and block the migratory activity of pancreatic tumor cells. The antitumor action is mediated through the NK-1 receptor. Thus, the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer and NK-1 receptor antagonists could improve pancreatic cancer treatment.