The Mechanisms of Glutathione S-Transferase M2 on Metastasis in Human Non-Small Cell Lung Cancer Cells

• Main Authors: Wan-Jung Yang, 楊宛蓉
• Other Authors: 柯俊良
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/21799291171747916227

碩士 === 中山醫學大學 === 醫學研究所 === 101 === Glutathione S-transferase Mu2 (GST-M2) is a phase II detoxification enzyme. Low expression of GST-M2 in lung cancers occurs due to hypermethylation of its promoter. Lung cancer with the GST mu-null genotype is also associated with shorter survival. However, a correlation between GST-M2 and important clinical parameters, as well as the migration of GST-M2 defective cells in lung cancer, has not been established. On the other hand, recent reports have found that nickel accumulation in lung cancer patient’s tissue. In our study, we investigate whether the reduction of GST-M2 was due to the GST-M2 promoter hypermethylation by nickel exposure and the role of GST-M2 in cell migration and actin disassembly in lung cancer cells. The expression of GST-M2 was decreased under NiCl2 exposure to 48 hours. The GST-M2 mRNA expression was restored in the CL1-0 cells under 5-aza-dC treatment. To investigate the correlation between GST-M2 and the mechanism of cell migration, the migration ability of overexpressed or silenced GST-M2 cancer cells was performed on wound healing and Boyden chamber assays. It reveals that the cell migration ability was inhibited in GST-M2 overexpressed cell line which depends on its enzymatic activity relative to control cancer cells. GST-M2 can induce connective tissue growth factor (CTGF) expression by driving the CTGF proximal promoter. Moreover, the cell migration was inhibited in the presence of r-hCTGF on GST-M2 silenced cells. With or without GST-M2 expression on tumor growth and metastasis were investigated in xenograft tumor model. Overexpression of GST-M2 dramatically reduced tumor growth and metastasis in a xenograft mice model. These data highlight that GST-M2 acts as a novel tumor suppressor by inhibiting cancer cell migration in lung cancer and animal models.