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本文引用的文献

1
The reverse Warburg effect is likely to be an Achilles' heel of cancer that can be exploited for cancer therapy.逆向Warburg效应可能是癌症的一个致命弱点，可被用于癌症治疗。
Oncotarget. 2017 May 25;8(34):57813-57825. doi: 10.18632/oncotarget.18175. eCollection 2017 Aug 22.
2
Dual Inhibition of HDAC and Tyrosine Kinase Signaling Pathways with CUDC-907 Inhibits Thyroid Cancer Growth and Metastases.CUDC-907 通过双重抑制组蛋白去乙酰化酶和酪氨酸激酶信号通路抑制甲状腺癌生长和转移。
Clin Cancer Res. 2017 Sep 1;23(17):5044-5054. doi: 10.1158/1078-0432.CCR-17-1043. Epub 2017 Jun 9.
3
Oxidative stress and apoptosis induction in human thyroid carcinoma cells exposed to the essential oil from Pistacia lentiscus aerial parts.暴露于乳香黄连木地上部分精油的人甲状腺癌细胞中的氧化应激和凋亡诱导
PLoS One. 2017 Feb 14;12(2):e0172138. doi: 10.1371/journal.pone.0172138. eCollection 2017.
4
Metformin targets multiple signaling pathways in cancer.二甲双胍作用于癌症中的多种信号通路。
Chin J Cancer. 2017 Jan 26;36(1):17. doi: 10.1186/s40880-017-0184-9.
5
Significance of OCT1 Expression in Acute Myeloid Leukemia.OCT1表达在急性髓系白血病中的意义
Pathol Oncol Res. 2017 Jul;23(3):665-671. doi: 10.1007/s12253-016-0161-7. Epub 2016 Dec 26.
6
Metformin reduces glycometabolism of papillary thyroid carcinoma in vitro and in vivo.二甲双胍在体外和体内均可降低甲状腺乳头状癌的糖代谢。
J Mol Endocrinol. 2017 Jan;58(1):15-23. doi: 10.1530/JME-16-0134.
7
Metformin: An anti-diabetic drug to fight cancer.二甲双胍：一种用于抗癌的抗糖尿病药物。
Pharmacol Res. 2016 Nov;113(Pt A):675-685. doi: 10.1016/j.phrs.2016.10.006. Epub 2016 Oct 5.
8
Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis.二甲双胍的使用可提高糖尿病肝癌患者的生存率：系统评价与荟萃分析。
Oncotarget. 2016 Oct 4;7(40):66202-66211. doi: 10.18632/oncotarget.11033.
9
Targeting Oct1 genomic function inhibits androgen receptor signaling and castration-resistant prostate cancer growth.靶向 Oct1 基因组功能抑制雄激素受体信号和去势抵抗性前列腺癌的生长。
Oncogene. 2016 Dec 8;35(49):6350-6358. doi: 10.1038/onc.2016.171. Epub 2016 Jun 6.
10
Metformin blocks progression of obesity-activated thyroid cancer in a mouse model.二甲双胍可阻断肥胖激活的小鼠甲状腺癌模型中的癌症进展。
Oncotarget. 2016 Jun 7;7(23):34832-44. doi: 10.18632/oncotarget.8989.

二甲双胍靶向线粒体甘油磷酸脱氢酶以控制甲状腺癌细胞的氧化磷酸化和生长速率。

Metformin Targets Mitochondrial Glycerophosphate Dehydrogenase to Control Rate of Oxidative Phosphorylation and Growth of Thyroid Cancer and .

机构信息

Metabolic Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland.

Endocrine Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland.

出版信息

Clin Cancer Res. 2018 Aug 15;24(16):4030-4043. doi: 10.1158/1078-0432.CCR-17-3167. Epub 2018 Apr 24.

DOI:10.1158/1078-0432.CCR-17-3167
PMID:29691295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6095745/
Abstract

Mitochondrial glycerophosphate dehydrogenase (MGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin in the liver. There are no data on the expression and role of MGPDH as a metformin target in cancer. In this study, we evaluated MGPDH as a potential target of metformin in thyroid cancer and investigated its contribution in thyroid cancer metabolism. We analyzed MGPDH expression in 253 thyroid cancer and normal tissues by immunostaining and examined its expression and localization in thyroid cancer-derived cell lines (FTC133, BCPAP) by confocal microscopy. The effects of metformin on MGPDH expression were determined by qRT-PCR and Western blot analysis. Seahorse analyzer was utilized to assess the effects of metformin on OXPHOS and glycolysis in thyroid cancer cells. We analyzed the effects of metformin on tumor growth and MGPDH expression in metastatic thyroid cancer mouse models. We show for the first time that MGPDH is overexpressed in thyroid cancer compared with normal thyroid. We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin and growth-inhibitory effects of metformin and Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin. .

摘要

线粒体甘油磷酸脱氢酶（MGPDH）是连接氧化磷酸化（OXPHOS）和糖酵解的关键酶，也是肝脏中抗糖尿病药物二甲双胍的靶点。目前尚无关于 MGPDH 作为二甲双胍在癌症中的靶点的表达和作用的相关数据。在这项研究中，我们评估了 MGPDH 作为甲状腺癌中二甲双胍的潜在靶点，并研究了其在甲状腺癌代谢中的作用。我们通过免疫染色分析了 253 例甲状腺癌和正常组织中的 MGPDH 表达，并通过共聚焦显微镜检查了甲状腺癌细胞系（FTC133、BCPAP）中 MGPDH 的表达和定位。通过 qRT-PCR 和 Western blot 分析确定了二甲双胍对 MGPDH 表达的影响。使用 Seahorse 分析仪评估了二甲双胍对甲状腺癌细胞 OXPHOS 和糖酵解的影响。我们分析了二甲双胍对转移性甲状腺癌小鼠模型中肿瘤生长和 MGPDH 表达的影响。我们首次表明，与正常甲状腺相比，MGPDH 在甲状腺癌中过度表达。我们证明 MGPDH 调节人甲状腺癌细胞生长和 OXPHOS 率。二甲双胍治疗与 MGPDH 表达下调和甲状腺癌细胞 OXPHOS 抑制有关。具有高 MGPDH 表达特征的细胞对二甲双胍的 OXPHOS 抑制作用和生长抑制作用更为敏感。我们的研究确立了 MGPDH 作为一种新型的甲状腺癌生长和代谢调节剂，可被二甲双胍有效靶向。