Focal adhesion kinase expression: A potential tumor therapy target

The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase implicated in cell cycle progression and migration. Over expression of FAK in a variety of tumors suggested that FAK is a promising target for therapeutic intervention. In this study, we took advantage of a modified polyethylenimine (M-PEI) with high transfection efficiency for tumor cells and tissues, and targeted FAK function through two approaches both in vitro) and in vivo. The results demonstrated that both the plasmid encoded FAK siRNA and over expressing of FAK-related non-kinase ( FRNK, FAK dominant negative) dramatically inhibited in vitro B16-F10 cells proliferation and invasion. For the purpose of evaluating the therapeutic potential of PEI-compelexed plasmids targeting FAK function, two transplantable mouse tumor models of primary and metastatic melanoma were adopted in this study, the results of which also revealed that intratumoral delivery of PEI-complexed plasmids targeting FAK significantly suppressed the primary tumor growth as well as the metastasis of B16-F10 cells into lung and lymph nodes. Both approaches protected the tumor-bearing mice with a prolonged survival. Taken together, these results indicated that intratumoral delivery of plasmid DNA targeting FAK function represents a promising avenue for melanoma therapy by using M-PEI as a gene carrier.