Effects Of Norepinephrine On The Proliferation And Migration Ability Of Lung Adenocarcinoma A549 Cells

Objective To explore the effects and the potential mechanism of norepinephrine on the proliferation and migration ability of lung adenocarcinoma A549 cells.Methods According to the treatment conditions, lung adenocarcinoma A549 cells were grouped as follows: control group(no intervention), norepinephrine groups(1, 10, 100 μmol/L norepinephrine), norepinephrine combined with propranolol group(10 μmol/L norepinephrine with 10 μmol/L propranolol), norepinephrine combined with carvedilol group(10 μmol/L norepinephrine with 10 μmol/L carvedilol), cisplatin groups(5, 10, 20, 40 μmol/L cisplatin), norepinephrine combined with cisplatin groups(10 μmol/L norepinephrine with 5, 10, 20, 40 μmol/L cisplatin). Proliferation rate was measured by MTT assay, migration ability was analyzed by wound scratch assay, the mRNA levels of vascular endothelial growth factor(VEGF) and matrix metalloproteinase-2(MMP-2) in A549 cells were observed by RT-PCR and the protein expression of VEGF and MMP-2 in supernatant was evaluated by ELISA. Then, the differences of A549 cells’ proliferation rate, migration ability, and the mRNA and protein levels of VEGF and MMP-2 among various groups were analyzed.Results There was no obvious difference in A549 cells’ proliferation rate among control group, norepinephrine groups, norepinephrine combined with propranolol group and norepinephrine combined with carvedilol group(P>0.05). Under the same intervention concentration of cisplatin, the A549 cells’ proliferation rates in groups of norepinephrine combined with cisplatin were significantly higher than cisplatin groups(P<0.05). Compared with the control group or norepinephrine combined with propranolol group or norepinephrine combined with carvedilol group, A549 cells in norepinephrine groups had stronger migration ability, upper-regulation of the mRNA levels of VEGF and MMP-2, and higher expression of proteins of VEGF and MMP-2(P<0.05). There was no significantly difference in the A549 cells’ migration ability or the mRNA levels of VEGF and MMP-2 or the expression of proteins of VEGF and MMP-2 among control group, norepinephrine combined with carvedilol group and norepinephrine combined with propranolol group(P>0.05).Conclusions Norepinephrine had no detectable effect on A549 cells’ proliferation rate. Norepinephrine might strengthen the migration ability of lung adenocarcinoma A549 cells through improving the expression of VEGF and MMP-2. The effects of norepinephrine on A549 cells’ migration ability and VEGF and MMP-2 expression could be inhibited by propranolol and carvedilol. Additionally, norepinephrine might weaken the effect of cisplatin on lung adenocarcinoma A549 cells’ proliferation.