title: Metformin reduces glycometabolism of papillary thyroid carcinoma in vitro and in vivo.
abstract: More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0-10 mM for 48 h)-treated cells by18F-FDG uptake assay and western blotting analysis, respectively. MicroPET/CT imaging was performed to detect18F-FDG uptake in vivo After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated.18F-FDG uptake reduced after metformin treatment in a dose-dependent manner, corresponding to the reduced expression level of HK2 and GLUT1 in vitro Xenograft model of PTC using BCPAP cells was achieved successfully. MicroPET/CT imaging showed that in vivo18F-FDG uptake decreased after treatment with metformin. Immunohistochemistry staining further confirmed the reduction of HK2 and GLUT1 expression in the tumor tissue of metformin-treated PTC xenograft model. In conclusion, metformin could reduce glucose metabolism of PTC in vitro and in vivo Metformin, by targeting glycometabolism of cancer cells, could be a promising adjuvant therapy alternative in the treatment modality of advanced thyroid carcinoma.
authors.affiliation: Department of Nuclear MedicineShanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.|Shanghai Jiao Tong University School of MedicineShanghai, People's Republic of China.
authors.forename: Chen-Tian
authors.initials: CT
authors.lastname: Shen
authors.affiliation: Department of Nuclear MedicineShanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Wei
authors.affiliation: Department of Nuclear MedicineShanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Zhong-Ling
authors.initials: ZL
authors.lastname: Qiu
authors.affiliation: Department of Nuclear MedicineShanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Song
authors.affiliation: Department of Nuclear MedicineShanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Nuclear MedicineShanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Zhen-Kui
authors.initials: ZK
authors.lastname: Sun
authors.affiliation: Department of Nuclear MedicineShanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China lqyn@sh163.net.
authors.forename: Quan-Yong
authors.initials: QY
authors.lastname: Luo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002291:Carcinoma, Papillary / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D064593:Heterografts; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D008687:Metformin / Q000494:pharmacology*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology
chemical_list: D051272:Glucose Transporter Type 1; D019788:Fluorodeoxyglucose F18; D008687:Metformin; D006593:Hexokinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: 18F-FDG uptake; glucose metabolism; metformin; papillary thyroid carcinoma