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.