Effects Of Propofol On Proliferation,Migration,and Wnt Signaling Pathway In Human Colon Cancer Cells With Different Degrees Of Differentiation In Vitro

Propofol is the most commonly used intravenous anesthetic.In recent years,more and more researches focus on propofol and tumor.Reports demonstrated that propofol has closely related with cell growth,proliferation,migration,invasion,metastasis and other behavior of many types of malignant tumors.Colorectal cancer(CRC)is one of the common malignant tumors in the digestive system.Statistic data showed that in 2015,the new morbidity and mortality of CRC in China ranked the fifth place.The occurrence and development of colon cancer is a complex process,the etiology and pathogenesis are not completely understood.Recent studies have found that the abnormal activation of Wnt/?-catenin signaling pathway is closely related to the growth,proliferation,migration and invasion of human colon cancer.Propofol has been reported to inhibit the invasion of human colon cancer LoVo cells,which is related to the downregulation of ERK1/2-dependent MMPs.The effect of propofol on the Wnt/?-catenin signaling in colon cancer cells has not been reported yet.In addition,we have not yet seen a comparative study of the effects of propofol on the biological functions(growth,proliferation,migration)of human colon cancer cells with different degrees of differentiation.Therefore,we investigated the effects of propofol on the growth and proliferation of Caco-2 and LoVo cells by selecting two colon cancer cell lines with different degrees of differentiation,Caco-2(well differentiated)and LoVo(low differentiation)by CCK-8 test;Transwell migration assay was used to detect the effect of propofol on the migration of Caco-2 and LoVo cells,and to find whether there was a difference between the sensitivity of propofol and colon cancer cells in different differentiation degree.Real-time PCR was used to detect the effect of propofol on Wntl and?-catenin mRNA expressions in Wnt/?-catenin signaling pathway in Caco-2 and LoVo cells.Western blot was used to detect the effect of propofol on Wntl,?-catenin protein expression.CCK-8 test results showed that propofol at a concentration of 6.25?100 ?g/mL could inhibit the growth of Caco-2 and LoVo cells in a time-and concentration-dependent manner.Compared with low-differentiated LoVo cells,well-differentiated Caco-2 cells are more sensitive to propofol.Transwell experiments showed that propofol at a concentration of 6.25?100 ?g/mL also inhibited the migration of Caco-2 and LoVo cells in a time-and-concentration-dependent manner.Caco-2 cells are more sensitive to propofol.Real-time PCR results showed that the mRNA expression levels of Wntl and P-catenin in Caco-2 and LoVo cells decreased in a concentration-dependent manner after treated with propofol at a concentration of 6.25?100 ?/mL,The effect of propofol on Wntl and ?-catenin mRNA expression in well-differentiated Caco-2 cells was more obvious.Western blot also showed that propofol at a concentration of 6.25-100 ?g/mL decreased the expression of Wntl and?-catenin protein in Caco-2 and LoVo cells in a concentration-dependent manner,Wntl and ?-catenin protein expression in well-differentiationed Caco-2 cells more obvious.Based on the above studies,we conclude that propofol inhibits the growth,proliferation and migration of human colon carcinoma Caco-2 and LoVo cells by decreasing the activation of Wnt/?-catenin signaling pathway.Well-differentiated human colon cancer cells Caco-2 are more sensitive to propofol.