Effect of propofol on RhoA/ROCK1 signaling pathway in human gastric cancer cells

Abstract

Objective To preliminarily evaluate the role of Ras homolog gene(Rho)/Rho-associated coiled coil-forming protein kinase(ROCK) signaling pathway in propofol-induced inhibition of metastasis of human gastric cancer cells. Methods Human gastric cancer MKN-45 cells cultured in vitro, with the concentration of 1.0×106 cells/ml, were seeded in culture plates, and incubated for 24 h. The plates were then randomly divided into 4 groups using a random number table: control group (group C), propofol group (group P), lysophosphatidic acid group (group L) and propofol + lysophosphatidic acid group (group PL). Group C received no administration.In group P, propofol at the final concentration of 16 μg/ml was given.In group L, lysophosphatidic acid at the final concentration of 1 μmol/L was administered.In group PL, propofol and lysophosphatidic acid were given with the final concentration of 16 μg/ml and 1 μmol/L, respectively.All the cells were then incubated for another 24 h. The migration of cells was determined by wound healing assay, and cell migration rates were calculated.The invasion of cells was determined by Transwell assay, and the invaded cells were counted.The expression of matrix metalloproteinases-2 (MMP-2), MMP-9, RhoA, and ROCK1 in cells was detected by Western blot. Results Compared with group C, cell migration rates and the number of invaded cells were significantly increased, and the expression of MMP-2, MMP-9, RhoA and ROCK1 was up-regulated in group L, and cell migration rates and the number of invaded cells were decreased, and the expression of MMP-2, MMP-9, RhoA and ROCK1 was down-regulated in group P. Compared with group L, cell migration rates and the number of invaded cells were significantly decreased, and the expression of MMP-2, MMP-9, RhoA and ROCK1 was down-regulated in group PL. Conclusion Inhibition of RhoA/ROCK1 signaling pathway is involved in the mechanism by which propofol decreases metastasis of human gastric cancer cells. Key words: Rho factor; rho-associated kinases; Propofol; Stomach neoplasms; Neoplasm metastasis