Monoacylglycerol lipase (MAGL) knockdown inhibits tumor cells growth in colorectal cancer

Objectives: Obesity has been reported to increase the risk of colorectal cancer, which may due to aberrant lipid metabolism. And recently findings of monoacylglycerol lipase provide a novel evidence in the correlation of obesity and cancer. So in this study, we investigated the effect of MAGL in regulation of tumor growth in colorectal cancer. Methods: MAGL expression in tumor tissues was estimated, and then JZL184 and siRNA were used to knockdown the expression of MAGL in colorectal cancer cells. Cell viability and invasion were detected to estimate the influence of MAGL knocked down in vitro and vivo. Then cell proliferation, apoptosis, cell cycle transition and screening of candidate genes were performed for further exploring of the effect mediated by MAGL knocked down. Results: It was noted that the expression of MAGL was highly elevated in tumor tissues, however, it was found only significantly correlated with the BMI index. Tumor cells' growth and invasion was significantly inhibited in vitro and in vivo induced by pharmacological and siRNA mediated MAGL knocked down. Cell proliferation was reduced and apoptosis was increased. And two target genes Cyclin D1 and Bcl-2 seemed to be repressed by MAGL knocked down. Conclusions: This study demonstrated colorectal cancer cells growth can be inhibited via knockdown of MAGL, which manipulate tumor cells proliferation and apoptosis by down-regulation of Cyclin D1 and Bcl-2. It provides a novel therapeutic target in treatment of colorectal cancer and a further support for the correlation of obesity and colorectal cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved.