Effects of nobiletin on proliferation,migration,and invasion of rectal cancer cells by regulating RAS/RAF/MEK/ERK signaling pathway
Objective To investigate the effects of nobiletin on the proliferation,migration,and invasion of rectal cancer cells by regulating the renin-angiotensin system(RAS)/RAF/mitogen-activated protein kinase(MEK)/extracellular regulated protein kinase(ERK)signaling pathway.Methods Human rectal cancer cells(SW480)were treated with nobiletin at concentrations of 5,10,20,40,and 80 μg·mL-1,and suitable experimental concentrations were screened.SW480 cells were randomly divided into control group,nobiletin low-,mid-,and high-doses(10,20,40 μg·mL-1)groups,and a high dose nobiletin+RAS activator group(RASAL1 group).The proliferation,migration,and invasion ability of SW480 cells were detected.Western blotting was applied to detect protein expression.Nude mice were used to detect the effect of nobiletin on rectal tumors.Results By screening the concentrations,concentrations of 10,20,and 40 μg·mL-1 of nobiletin were selected for the experiment.Compared with the control group,the Edu positive rate,cell invasion number,and scratch healing rate decreased in the nobiletin groups,while the expression levels of cyclin-dependent kinase 1(CDK1),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),RAS,RAF,MEK,and ERK decreased(P<0.05).Compared with nobiletin high dose group,the Edu positive rate,cell invasion number,and scratch healing rate increased in the nobiletin+RASAL1 group,while the expression levels of CDK1,MMP-2,MMP-9,RAS,RAF,MEK,and ERK(P<0.05).The growth rate of transplanted tumors in the nobiletin groups was slower than that in the control group,the tumor volume decreased,the quality decreased,and the expression of RAS,RAF,MEK,and ERK proteins was down regulated(P<0.05).Conclusion Nobiletin inhibits the activation of the RAS/RAF/MEK/ERK signaling pathway,thereby inhibiting the proliferation,migration,and invasion of rectal cancer cells.
rectal cancernobiletinRAS/RAF/mitogen-activated protein kinase(MEK)/extracellular regulated protein kinase(ERK)signaling pathwayproliferationmigrationinvasion