Effect of oxycodone on migration of human colon cancer cells : the role of μ and κ receptors / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of oxycodone on migration of human colon cancer cells and the role of μ and κ receptors.Methods The human colon cancer HCT116 cells at the logarithmic growth phase were seeded in 24-well or in 6-well plates at a density of 1 × 106 cells/mnl (0.5 ml/well or 2 ml/well,144 wells in total).The cells were divided into 6 groups (n=24 each) using a random number table:control group (group C),1,5 and 10 μmol/L oxycodone groups (group O1,group O2 and group O3),oxycodone plus μ receptor antagonist CTOP group (group O2+CTOP) and oxycodone plus κ receptor antagonist nor-binaltorphimine group (group O2+BNI).The cells were incubated for 24 h with oxycodone 1,5 and 10 μmol/L in O1,O2 and O3 groups,respectively.The cells were incubated for 24 h with 5 μmol/L oxycodone plus 20 μmol/L CTOP and 5 μmol/L oxycodone plus nor-binahorphimin 20 μmol/L in O2+CTOP and O2+BNI groups,respectively.The invaded and migrated cells were counted,and the levels of Ras homolog gene family member A (RhoA),Rho-associated protein kinase 1 (ROCK1),matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected.Results Compared with group C,the number of invaded and migrated cells was gradually decreased,and the levels of RhoA,ROCK1,MMP-2 and MMP9 were gradually decreased in O1,O2 and O3 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group O2+BNI (P＞0.05).Compared with group O2,the number of invaded and migrated cells was significantly increased,and the levels of RhoA,ROCK1,MMP-2 and MMP9 were increased in group O2 + BNI (P＜0.05),and no significant change was found in the parameters mentioned above in group O2+CTOP (P＞0.05).Conclusion Oxyc odone can inhibit the migration of human colon cancer cells,and the mechanism is totally related to inhibition of RhoA/ROCKl signaling pathway activation after activating κ receptors,but not related to μ receptors.