Oncotarget

Research Papers:

Synergistic inhibition of colon cancer growth by the combination of methylglyoxal and silencing of glyoxalase I mediated by the STAT1 pathway

Yuan Chen, Lei Fang, Gefei Li, Jiali Zhang, Changxi Li, Mengni Ma, Chen Guan, Fumao Bai, Jianxin Lyu _ and Qing H. Meng

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Oncotarget. 2017; 8:54838-54857. https://doi.org/10.18632/oncotarget.18601

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Abstract

Yuan Chen1,*, Lei Fang1,*, Gefei Li1, Jiali Zhang1, Changxi Li1, Mengni Ma1, Chen Guan1, Fumao Bai1, Jianxin Lyu1 and Qing H. Meng2

1Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China

2Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

*These authors have contributed equally to this work

Correspondence to:

Jianxin Lyu, email: [email protected]

Qing H. Meng, email: [email protected]

Keywords: colon cancer, methylglyoxal, glyoxalase I, synergistic inhibition, STAT1

Received: February 06, 2017     Accepted: May 31, 2017     Published: June 22, 2017

ABSTRACT

Methylglyoxal (MG), an extremely reactive glucose metabolite, exhibits antitumor activity. Glyoxalase I (GLOI), which catalyzes MG metabolism, is associated with the progression of human malignancies. While the roles of MG or GLOI have been demonstrated in some types of cancer, their effects in colon cancer and the mechanisms underlying these effects remain largely unknown. For this study, MG and GLOI levels were manipulated in colon cancer cells and the effects on their viability, proliferation, apoptosis, migration, and invasion in vitro were quantified by Cell Counting Kit-8, colony formation assay, flow cytometry, and transwell assays. The expression levels of STAT1 pathway–associated proteins and mRNAs in these cells were quantified by western blot and qRT-PCR, respectively. The antitumor effects of MG and silencing of GLOI were investigated in vivo in a SW620 colon cancer xenograft model in BALB/c nude mice. Our findings demonstrate that MG in combination with silencing of GLOI synergistically inhibited the cancer cells’ proliferation, colony formation, migration, and invasion and induced apoptosis in vitro compared with the controls. Furthermore, these treatments up-regulated STAT1 and Bax while down-regulating Bcl-2 in vitro. MG treatment alone or in combination with silencing of GLOI also reduced the growth of the SW620 tumors in mice by up-regulation of STAT1 and Bax and down-regulation of Bcl-2. Taken together, our findings suggest that MG in combination with silencing of GLOI merits further evaluation as a targeted therapeutic strategy for colon cancer.


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