Additive effects of eukaryotic co-expression plasmid carrying GRIM-19 and LKB1 genes on breast cancer in vitro and in vivo

摘要

Gene associated with retinoid-interferon-induced mortality 19 (GRIM-19) and the liver kinase B1 (LKB1) gene, two types of tumor suppressor gene, have been demonstrated to have important roles in breast carcinogenesis. The present study developed a dual expression plasmid that co-expressed GRIM-19 and LKB1, and evaluated the combined effects of the two genes against breast cancer in vitro and in vivo. Transfection with a plasmid for the simultaneous expression of GRIM-19 and LKB1 (pGRIM19-LKB1) into MCF-7 breast cancer cells significantly inhibited the proliferation, colony formation, migration and invasion compared with the effects of transfection with either pGRIM-19 or pLKB1 alone. Furthermore, transfection with pGRIM19-LKB1 induced enhanced levels of apoptosis and cell cycle arrest at G0/G1 stage in MCF7 cells compared to the effects of pGRIM-19 or pLKB1 alone. An in vivo experiment using an MCF-7 xenograft tumor model demonstrated that intravenous injection of pGRIM19-LKB1 had an enhanced effect on tumor growth inhibition compared to that of pGRIM-19 or pLKB1 alone. In conclusion the findings of the present study suggested that transfection with eukaryotic plasmid for the simultaneous expression of GRIM-19 and LKB1 more effectively suppressed the growth of breast cancer in vitro and in vivo, and may therefore have therapeutic potential for the treatment of human breast cancer.