Mechanism study of high OATP1B3 expression in hepatocellular carcinoma to enhance the efficacy of Sorafenib
Objective To explore the enhancement effect of high OATP1B3 expression in hepato⁃cellular carcinoma(HCC)on sorafenib and its related mechanisms.Methods The study selected 48 liver can⁃cer patients admitted to the First Affiliated Hospital of Fujian Medical University from January 2016 to Decem⁃ber 2018 as research subjects.The aim was to observe the expression of OATP1B3 in liver cancer tissue and ad⁃jacent tissues 2 cm from the tumor edge,and to investigate the impact of OATP1B3 expression on the survival of patients receiving sorafenib treatment.High expression of OATP1B3 in transfected Hep⁃1 cells was exam⁃ined,along with an analysis of the relevant signaling pathways involved in the expression of OATP1B3,and biological behavior effects of sorafenib on OATP1B3 high expression tumor cells were explored through trans⁃fection of tumor cells.Results The mRNA expression,protein expression level and immunohistochemical score of OATP1B3 in cancer tissues of 48 patients with liver cancer were lower than those in adjacent tissues,and the differences were statistically significant(P<0.05).The proliferation,migration and invasion abilities of Hep⁃1 cells transfected with OATP1B3 were lower than those of negative control cells,and the difference was statisti⁃cally significant(P<0.05).In Hep⁃1 cells transfected with OATP1B3,the expressions of N⁃cadherin,Vimentin,β⁃catenin,CD33,OCT4,NANOG and SOX⁃2 in Bcl2 stem cell⁃like cells were down⁃regulated,while the ex⁃pressions of E⁃cadherin,BAX and C⁃caspase3 were up⁃regulated.The apoptosis rate was higher than that of nega⁃tive control cells.After treatment with sorafenib,the growth and activity of tumor cells with high OATP1B3 ex⁃pression were decreased.In HCC patients treated with sorafenib,the survival time of patients with high OATP1B3 expression was significantly prolonged.The expression level of OATP1B3 could be used as an independent risk factor for predicting the survival time of patients taking sorafenib(P<0.05).Conclusion The high expression of OATP1B3 in hepatocellular carcinoma tissues can effectively enhance the efficacy of sorafenib and inhibit the de⁃velopment of cancer.This provides a theoretical basis for optimizing related treatment regimens.
Hepatocellular carcinomaOATP1B3 geneSorafenibMechanism research
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维普
