Chen Yuan, Fang Lei, Li Gefei, Zhang Jiali, Li Changxi, Ma Mengni, Guan Chen, Bai Fumao, Lyu Jianxin, Meng Qing H
Key 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.
Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Oncotarget. 2017 Jun 22;8(33):54838-54857. doi: 10.18632/oncotarget.18601. eCollection 2017 Aug 15.
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 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 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 compared with the controls. Furthermore, these treatments up-regulated STAT1 and Bax while down-regulating Bcl-2 . 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.
甲基乙二醛（MG）是一种极具反应性的葡萄糖代谢产物，具有抗肿瘤活性。催化MG代谢的乙二醛酶I（GLOI）与人类恶性肿瘤的进展相关。虽然MG或GLOI的作用已在某些类型的癌症中得到证实，但其在结肠癌中的作用以及这些作用的潜在机制仍 largely未知。在本研究中，在结肠癌细胞中调控MG和GLOI水平，并通过细胞计数试剂盒-8、集落形成试验、流式细胞术和Transwell试验对其对细胞活力、增殖、凋亡、迁移和侵袭的影响进行定量。分别通过蛋白质印迹法和qRT-PCR对这些细胞中STAT1信号通路相关蛋白和mRNA的表达水平进行定量。在BALB/c裸鼠的SW620结肠癌异种移植模型中研究了MG和GLOI沉默的抗肿瘤作用。我们的研究结果表明，与对照组相比，MG联合GLOI沉默可协同抑制癌细胞的增殖、集落形成、迁移和侵袭，并诱导凋亡。此外，这些处理上调了STAT1和Bax，同时下调了Bcl-2。单独使用MG或与GLOI沉默联合使用也通过上调STAT1和Bax以及下调Bcl-2来减少小鼠体内SW620肿瘤的生长。综上所述，我们的研究结果表明，MG联合GLOI沉默作为结肠癌的靶向治疗策略值得进一步评估。
