Background:Hepatocellular carcinoma(HCC)is a common disease in human history and one of the main causes of cancer-related death.Insufficient oxygen supply in the tumor microenvironment forces cancer cells to survive i...Background:Hepatocellular carcinoma(HCC)is a common disease in human history and one of the main causes of cancer-related death.Insufficient oxygen supply in the tumor microenvironment forces cancer cells to survive in a mild hypoxia environment.Fibroblast growth factor 21(FGF21),a member of the FGF family,has become the focus of public attention due to its outstanding achievements in diabetes and lipid lowering.However,the mechanism of FGF21 in HCC remains unclear.Objective:The aims of this study were to clarify whether or not FGF21 could increase the sensitivity of HCC to sorafenib(SORA)under hypoxia and explore the possible mechanism.Methods:In this study,by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide cell viability test,plate clone formation test,western blot analysis,Hoechst/propidium iodide double staining experiment,flow cytometry,quantitative reverse transcription polymerase chain reaction,and subcutaneous tumor transplantation in mice,we studied the effects of recombinant human FGF21 combined with SORA on hepatoma cells in vitro and in vivo.FGF21 could enhance the phosphorylation of mothers against decapentaplegic homolog 3(Smad3)under anaerobic conditions.When combined with SORA,FGF21 could increase the sensitivity of hepatoma cells to SORA and inhibit the growth and migration of hepatoma cells.Results:FGF21 may increase the sensitivity of HCC to SORA by enhancing the phosphorylation of Smad3 through the phosphatidylinositol 3-kinase/protein kinase B pathway under hypoxia.Conclusion:Our study suggested the possibility of combination therapy for SORA and FGF21 on HCC.展开更多
基金National Natural Science Foundation of China(Grant No.81101570)Wenzhou Municipal Science and Technology Bureau(Grant No.Y2020146)Scientific Research Fund of Zhejiang Provincial Education Department of China(Grant No.Y201942205).
文摘Background:Hepatocellular carcinoma(HCC)is a common disease in human history and one of the main causes of cancer-related death.Insufficient oxygen supply in the tumor microenvironment forces cancer cells to survive in a mild hypoxia environment.Fibroblast growth factor 21(FGF21),a member of the FGF family,has become the focus of public attention due to its outstanding achievements in diabetes and lipid lowering.However,the mechanism of FGF21 in HCC remains unclear.Objective:The aims of this study were to clarify whether or not FGF21 could increase the sensitivity of HCC to sorafenib(SORA)under hypoxia and explore the possible mechanism.Methods:In this study,by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide cell viability test,plate clone formation test,western blot analysis,Hoechst/propidium iodide double staining experiment,flow cytometry,quantitative reverse transcription polymerase chain reaction,and subcutaneous tumor transplantation in mice,we studied the effects of recombinant human FGF21 combined with SORA on hepatoma cells in vitro and in vivo.FGF21 could enhance the phosphorylation of mothers against decapentaplegic homolog 3(Smad3)under anaerobic conditions.When combined with SORA,FGF21 could increase the sensitivity of hepatoma cells to SORA and inhibit the growth and migration of hepatoma cells.Results:FGF21 may increase the sensitivity of HCC to SORA by enhancing the phosphorylation of Smad3 through the phosphatidylinositol 3-kinase/protein kinase B pathway under hypoxia.Conclusion:Our study suggested the possibility of combination therapy for SORA and FGF21 on HCC.
