Choline suppresses hepatocellular carcinoma progression by attenuating AMPK/mTOR-mediated autophagy via choline transporter SLC5A7 activation  

作　　者：Chen Wang Zhao-Yan Liu Wen-Ge Huang Zhi-Jun Yang Qiu-Ye Lan Ai-Ping Fang Meng-Jun Hou Xiao-Lin Luo Yao-Jun Zhang Si Chen Hui-Lian Zhu 

机构地区：[1]Department of Nutrition,School of Public Health,Sun Yat-sen University,Guangzhou,China [2]Guangdong Provincial Key Laboratory of Food,Nutrition and Health,School of Public Health,Sun Yat-sen University,Guangzhou,China [3]Center of Experimental Animals,Sun Yat-sen University,Guangzhou,China [4]Experimental and Teaching Center for Public Health,School of Public Health,Sun Yat-sen University,Guangzhou,China [5]Department of Hepatobiliary Oncology,Sun Yat-sen University Cancer Center,Guangzhou,China

出　　处：《Hepatobiliary Surgery and Nutrition》2024年第3期393-411,I0001,I0002,共21页肝胆外科与营养（英文）

基　　金：Basic and Applied Basic Research Foundation of Guangdong Province,China(grant No.2020A1515110682);Guangdong Provincial Science and Technology Project(grant No.2017A040406008);National Natural Science Foundation of China(grant Nos.81973016,82103825);Postdoctoral Science Foundation of China(grant No.2020M683135).

摘　　要：Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-associated death.Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis,metastasis,and prognosis.Choline is an essential nutrient related to prolonged survival and reduced risk of HCC.However,it remains unclear whether this phenomenon is mediated by autophagy.Methods:Two HCC cell lines(HUH-7 and Hep3B)were used in the present study.Cell growth was evaluated by cell counting kit 8(CCK-8),colony formation,and in vivo mouse xenografts assays.Cell motility was calculated by wound healing and transwell assays.Autophagosomes were measured by transmission electron microscope(TEM),and autophagy flux was detected by mRFP-GFP-labeled LC3 protein.The mRNA level of genes was measured by quantitative real-time polymerase chain reaction(qRT-PCR).The protein levels were detected by Western blotting(WB).Results:We found that choline inhibited the proliferation,migration,and invasion of HCC cells by downregulating autophagy in vitro and in vivo.Upregulated expression of the solute carrier family 5 member 7(SLC5A7),a specific choline transporter,correlated with better HCC prognosis.We further discovered that choline could promote SLC5A7 expression,upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway,and attenuate autophagy.Finally,we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo.Conclusions:Our findings provide novel insights into choline-mediated autophagy in HCC,providing the foothold for its future application in HCC treatment.

关 键 词：Hepatocellular carcinoma(HCC) AUTOPHAGY CHOLINE solute carrier family 5 member 7(SLC5A7) 

分 类 号：R735.7[医药卫生—肿瘤]