Alteration of Cholesterol Metabolism by Metformin Is Associated With Improved Outcome in Type II Diabetic Patients With Diffuse Large B-Cell Lymphoma

被引：12

作者：

Jiang, Xiang-Nan ^{[1
,2
]}

Zhang, Yan ^{[1
,2
]}

Wang, Wei-Ge ^{[1
,2
]}

Sheng, Dong ^{[1
,2
]}

Zhou, Xiao-Yan ^{[1
,2
]}

Li, Xiao-Qiu ^{[1
,2
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 11卷

关键词：

metformin; cholesterol; diffuse large B-cell lymphoma; B-cell receptor; type II diabetes; LIPID RAFTS; CANCER; AMPK; RISK; INSIGHTS; SUBTYPES;

D O I：

10.3389/fonc.2021.608238

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recent studies have demonstrated the benefits of metformin on patients with lymphomas. B-cell receptor (BCR)-PI3K-AKT pathway-dependent cholesterol synthesis may represent a positive feedback mechanism responsible for the pathogenesis of BCR-dependent diffuse large B-cell lymphomas (DLBCLs). Thus, restriction of lipid synthesis would affect the integrity of lipid-forming membranes and block the BCR signaling pathway. Our in vitro findings suggested that the blocking effect of metformin on BCR signaling pathway is possibly exerted via blocking the biosynthesis of cholesterol. A retrospective case-control study was subsequently conducted on type II diabetic patients with DLBCL who were on metformin. Metformin was identified to be associated with improved response rate and PFS in diabetic patients and appeared to be an effective therapeutic drug against DLBCL.

引用

页数：7

共 30 条

[1] Anticancer activity of metformin: a systematic review of the literature [J].

Aljofan, Mohamad ;

Riethmacher, Dieter .

FUTURE SCIENCE OA, 2019, 5 (08)

[2] Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma [J].

Caro, Pilar ;

Kishan, Amar U. ;

Norberg, Erik ;

Stanley, Illana A. ;

Chapuy, Bjoern ;

Ficarro, Scott B. ;

Polak, Klaudia ;

Tondera, Daniel ;

Gounarides, John ;

Yin, Hong ;

Zhou, Feng ;

Green, Michael R. ;

Chen, Linfeng ;

Monti, Stefano ;

Marto, Jarrod A. ;

Shipp, Margaret A. ;

Danial, Nika N. .

CANCER CELL, 2012, 22 (04) :547-560

[3] Association between metformin use and progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus: a population-based retrospective cohort study [J].

Chang, Su-Hsin ;

Luo, Suhong ;

O'Brian, Katiuscia K. ;

Thomas, Theodore S. ;

Colditz, Graham A. ;

Carlsson, Nils P. ;

Carson, Kenneth R. .

LANCET HAEMATOLOGY, 2015, 2 (01) :E30-E36

[4] Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes [J].

Chapuy, Bjoern ;

Stewart, Chip ;

Dunford, Andrew J. ;

Kim, Jaegil ;

Kamburov, Atanas ;

Redd, Robert A. ;

Lawrence, Mike S. ;

Roemer, Margaretha G. M. ;

Li, Amy J. ;

Ziepert, Marita ;

Staiger, Annette M. ;

Wala, Jeremiah A. ;

Ducar, Matthew D. ;

Leshchiner, Ignaty ;

Rheinbay, Ester ;

Taylor-Weiner, Amaro ;

Coughlin, Caroline A. ;

Hess, Julian M. ;

Pedamallu, Chandra S. ;

Livitz, Dimitri ;

Rosebrock, Daniel ;

Rosenberg, Mara ;

Tracy, Adam A. ;

Horn, Heike ;

van Hummelen, Paul ;

Feldman, Andrew L. ;

Link, Brian K. ;

Novak, Anne J. ;

Cerhan, James R. ;

Habermann, Thomas M. ;

Siebert, Reiner ;

Rosenwald, Andreas ;

Thorner, Aaron R. ;

Meyerson, Matthew L. ;

Golub, Todd R. ;

Beroukhim, Rameen ;

Wulf, Gerald G. ;

Ott, German ;

Rodig, Scott J. ;

Monti, Stefano ;

Neuberg, Donna S. ;

Loeffler, Markus ;

Pfreundschuh, Michael ;

Truemper, Lorenz ;

Getz, Gad ;

Shipp, Margaret A. .

NATURE MEDICINE, 2018, 24 (05) :679-+

[5] SYK Inhibition Modulates Distinct PI3K/AKT-Dependent Survival Pathways and Cholesterol Biosynthesis in Diffuse Large B Cell Lymphomas [J].

Chen, Linfeng ;

Monti, Stefano ;

Juszczynski, Przemyslaw ;

Ouyang, Jing ;

Chapuy, Bjoern ;

Neuberg, Donna ;

Doench, John G. ;

Bogusz, Agata M. ;

Habermann, Thomas M. ;

Dogan, Ahmet ;

Witzig, Thomas E. ;

Kutok, Jeffery L. ;

Rodig, Scott J. ;

Golub, Todd ;

Shipp, Margaret A. .

CANCER CELL, 2013, 23 (06) :826-838

[6] Effect of metformin use on the risk and prognosis of endometrial cancer: a systematic review and meta-analysis [J].

Chu, Danxia ;

Wu, Jie ;

Wang, Kaili ;

Zhao, Mengling ;

Wang, Chunfang ;

Li, Liuxia ;

Guo, Ruixia .

BMC CANCER, 2018, 18

[7] Poor Concordance among Nine Immunohistochemistry Classifiers of Cell-of-Origin for Diffuse Large B-Cell Lymphoma: Implications for Therapeutic Strategies [J].

Coutinho, Rita ;

Clear, Andrew James ;

Owen, Andrew ;

Wilson, Andrew ;

Matthews, Janet ;

Lee, Abigail ;

Alvarez, Rute ;

da Silva, Maria Gomes ;

Cabecadas, Jose ;

Calaminici, Maria ;

Gribben, John G. .

CLINICAL CANCER RESEARCH, 2013, 19 (24) :6686-6695

[8] Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis [J].

DeCensi, Andrea ;

Puntoni, Matteo ;

Goodwin, Pamela ;

Cazzaniga, Massimiliano ;

Gennari, Alessandra ;

Bonanni, Bernardo ;

Gandini, Sara .

CANCER PREVENTION RESEARCH, 2010, 3 (11) :1451-1461

[9] Location is everything: Lipid rafts and immune cell signaling [J].

Dykstra, M ;

Cherukuri, A ;

Sohn, HW ;

Tzeng, SJ ;

Pierce, SK .

ANNUAL REVIEW OF IMMUNOLOGY, 2003, 21 :457-481

[10] AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo [J].

Faubert, Brandon ;

Boily, Gino ;

Izreig, Said ;

Griss, Takla ;

Samborska, Bozena ;

Dong, Zhifeng ;

Dupuy, Fanny ;

Chambers, Christopher ;

Fuerth, Benjamin J. ;

Viollet, Benoit ;

Mamer, Orval A. ;

Avizonis, Daina ;

DeBerardinis, Ralph J. ;

Siegel, Peter M. ;

Jones, Russell G. .

CELL METABOLISM, 2013, 17 (01) :113-124

← 1 2 3 →