Norepinephrine-induced invasion by pancreatic cancer cells is inhibited by propranolol.
Active migration and invasion by cancer cells are a prerequisite for the development of metastases. Recent studies have shown that neurotransmitters are involved in the regulation of cancer cell invasion via beta-adrenoceptors (beta-ARs). However, little is known regarding the effect of neurotransmitters on pancreatic cancer cells. The aim of our study was to examine the regulative effect of norepinephrine (NE), which belongs to the group of classical neurotransmitters, on the invasiveness of pancreatic cancer cells and the therapeutic effect of the beta-blocker, propranolol, on them. The human pancreatic cancer cell lines, Miapaca-2 and Bxpc-3, were selected for this study, and in both cell lines, beta1-AR and beta2-AR expression was determined by RT-PCR and Western blotting. The invasiveness of pancreatic cancer cells was examined using the Matrigel invasion assay. The concentrations of MMP-2, MMP-9, and VEGF in the culture medium and in the cancer cells were examined by ELISA and RT-PCR, respectively. We observed that NE promoted the invasiveness of Miapaca-2 cells in a concentration-dependent manner, and NE increased the expression of MMP-2, MMP-9, and VEGF. However, these effects could be inhibited by the beta-blocker, propranolol. In conclusion, the development of metastases is not only genetically determined, but is also influenced by NE, which is one of the signal substances present in the tumor environment. This study also provides experimental evidence for the use of beta-blockers in the chemoprevention of pancreatic cancer metastasis.
Guo
Kun
K
Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
Ma
Qingyong
Q
Wang
Liancai
L
Hu
Hengtong
H
Li
Junhui
J
Zhang
Dong
D
Zhang
Min
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009638:Norepinephrine / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011433:Propranolol / Q000494:pharmacology*; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D042461:Vascular Endothelial Growth Factor A; D011433:Propranolol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009638:Norepinephrine