Guo Yi, Zhang Yuning, Yang Xunjun, Lu Panpan, Yan Xijuan, Xiao Fanglan, Zhou Huaibin, Wen Chaowei, Shi Mengru, Lu Jianxin, Meng Qing H
a 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 , China.
b Department of Laboratory Medicine , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
Cancer Biol Ther. 2016;17(2):169-80. doi: 10.1080/15384047.2015.1121346. Epub 2015 Nov 30.
Emerging evidence indicates that methylglyoxal (MG) can inhibit tumorigenesis. Glyoxalase I (GLOI), a MG degradation enzyme, is implicated in the progression of human malignancies. However, little is known about the roles of MG and GLOI in breast cancer. Our purpose was to investigate the anticancer effects of MG and inhibition of GLOI on breast cancer cells and the underlying mechanisms of these effects. Our findings demonstrate that cell viability, migration, invasion, colony formation, and tubule formation were significantly restrained by addition of MG or inhibition of GLOI, while apoptosis was significantly increased. Furthermore, the expression of p-JNK, p-ERK, and p-p38 was markedly upregulated by addition of MG or inhibition of GLOI, whereas MMP-9 and Bcl-2 expression levels were dramatically decreased. These effects were augmented by combined treatment with MG and inhibition of GLOI. Collectively, these data indicate that MG or inhibition of GLOI induces anticancer effects in breast cancer cells and that these effects are potentiated by combination of the 2. These effects were modulated by activation of the MAPK family and downregulation of Bcl-2 and MMP-9. These findings may provide a new approach for the treatment of breast cancer.
新出现的证据表明，甲基乙二醛（MG）可抑制肿瘤发生。乙二醛酶I（GLOI）是一种MG降解酶，与人类恶性肿瘤的进展有关。然而，关于MG和GLOI在乳腺癌中的作用知之甚少。我们的目的是研究MG的抗癌作用以及抑制GLOI对乳腺癌细胞的影响及其潜在机制。我们的研究结果表明，添加MG或抑制GLOI可显著抑制细胞活力、迁移、侵袭、集落形成和小管形成，同时细胞凋亡显著增加。此外，添加MG或抑制GLOI可显著上调p-JNK、p-ERK和p-p38的表达，而MMP-9和Bcl-2的表达水平则显著降低。MG与抑制GLOI联合治疗可增强这些效应。总体而言，这些数据表明，MG或抑制GLOI可在乳腺癌细胞中诱导抗癌作用，且二者联合可增强这些作用。这些作用通过丝裂原活化蛋白激酶（MAPK）家族的激活以及Bcl-2和MMP-9的下调来调节。这些发现可能为乳腺癌的治疗提供一种新方法。
