Chemopreventive Effects of Pioglitazone on Chemically Induced Lung Carcinogenesis in Mice

被引：39

作者：

Wang, Yian ^{[1
,3
]}

James, Michael ^{[1
,3
]}

Wen, Weidong ^{[1
,3
]}

Lu, Yan ^{[1
,3
]}

Szabo, Eva ^{[2
]}

Lubet, Ronald A. ^{[2
]}

You, Ming ^{[1
,3
]}

机构：

[1] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA

[2] NCI, Canc Prevent Div, Bethesda, MD 20892 USA

[3] Washington Univ, Alvin J Siteman Canc Ctr, Sch Med, St Louis, MO 63110 USA

来源：

MOLECULAR CANCER THERAPEUTICS | 2010年 / 9卷 / 11期

关键词：

ACTIVATED RECEPTOR-GAMMA; SQUAMOUS-CELL CARCINOMA; PPAR-GAMMA; A/J MICE; COLON CARCINOGENESIS; TRANSGENIC MICE; BREAST-CANCER; CHINESE HERBS; MOUSE MODELS; P53;

D O I：

10.1158/1535-7163.MCT-10-0510

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pioglitazone [(RS)-5-(4-[2-(5-ethylpyridin-2-yl) ethoxy] benzyl) thiazolidine-2,4-dione] is a ligand of nuclear receptor peroxisome proliferator-activated receptor. that is approved for the treatment of type II diabetes mellitus. Activation of peroxisome proliferator-activated receptor. has been associated with anticancer activities in a variety of cancer cell lines through inhibition of proliferation and promotion of apoptosis. We examined the effect of pioglitazone on lung cancer development in carcinogen-induced lung adenocarcinoma and squamous cell carcinoma (SCC). When pioglitazone was administered beginning 8 weeks after the first carcinogen treatment when microscopic adenomas already existed, pioglitazone significantly inhibited tumor load (sum of tumor volume per lung in average) by 64% (P < 0.05) in p53(wt/wt) mice and 50% (P < 0.05) in p53(wt/Ala135Val) mice in the lung adenocarcinoma model. Delayed administration of pioglitazone caused a limited (35%, P < 0.05) decrease in lung SCC. Induction of apoptosis occurred in both model systems. These data show that pioglitazone significantly inhibited progression of both adenocarcinoma and SCC in the two mouse model systems. Mol Cancer Ther; 9(11); 3074-82. (C) 2010 AACR.

引用

页码：3074 / 3082

页数：9

共 46 条

[1]

BOONE CW, 1990, CANCER RES, V50, P2

[2]

Chang TH, 2000, CANCER RES, V60, P1129

[3] Alterations in thigh subcutaneous adipose tissue gene expression in protease inhibitor-based highly active antiretroviral therapy [J].

Chaparro, J ;

Reeds, DN ;

Wen, WD ;

Xueping, E ;

Klein, S ;

Semenkovich, CF ;

Bae, KT ;

Quirk, EK ;

Powderly, WG ;

Yarasheski, KE ;

Li, E .

METABOLISM-CLINICAL AND EXPERIMENTAL, 2005, 54 (05) :561-567

[4] Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events):: a randomised controlled trial [J].

Dormandy, JA ;

Charbonnel, B ;

Eckland, DJA ;

Erdmann, E ;

Massi-Benedetti, M ;

Kmoules, IK ;

Skene, AM ;

Tan, MH ;

Lefébvre, PJ ;

Murray, GD ;

Standl, E ;

Wilcox, RG ;

Wlhelmsen, L ;

Betteridge, J ;

Birkeland, K ;

Golay, A ;

Heine, RJ ;

Korányi, L ;

Laakso, M ;

Mokán, M ;

Norkus, A ;

Pirags, V ;

Podar, T ;

Scheen, A ;

Scherbaum, W ;

Schernthaner, G ;

Schmitz, O ;

Skrha, J ;

Smith, U ;

Taton, J .

LANCET, 2005, 366 (9493) :1279-1289

[5] Ligands for peroxisome proliferator-activated receptorγ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice [J].

Elstner, E ;

Müller, C ;

Koshizuka, K ;

Williamson, EA ;

Park, D ;

Asou, H ;

Shintaku, P ;

Said, JW ;

Heber, D ;

Koeffler, HP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8806-8811

[6]

Eshleman JS, 2002, CANCER RES, V62, P7291

[7] APIC-dependent suppression of colon carcinogenesis by PPARγ [J].

Girnun, GD ;

Smith, WM ;

Drori, S ;

Sarraf, P ;

Mueller, E ;

Eng, C ;

Nambiar, P ;

Rosenberg, DW ;

Bronson, RT ;

Edelmann, W ;

Kucherlapati, R ;

Gonzalez, FJ ;

Spiegelman, BM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (21) :13771-13776

[8] Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes [J].

Govindarajan, Rangaswamy ;

Ratnasinghe, Luke ;

Simmons, Debra L. ;

Siegel, Eric R. ;

Midathada, Madhu V. ;

Kim, Lawrence ;

Kim, Peter J. ;

Owens, Randall J. ;

Lang, Nicholas P. .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (12) :1476-1481

[9]

Guo YT, 2004, WORLD J GASTROENTERO, V10, P3419

[10] RGS17, an Overexpressed Gene in Human Lung and Prostate Cancer, Induces Tumor Cell Proliferation Through the Cyclic AMP-PKA-CREB Pathway [J].

James, Michael A. ;

Lu, Yan ;

Liu, Yan ;

Vikis, Haris G. ;

You, Ming .

CANCER RESEARCH, 2009, 69 (05) :2108-2116

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